The process of liver regeneration after partial hepatectomy is very complex and is associated with signalling cascades involving initiation signals, transcription factors, cytokines, growth factors, tissue remodelling and termination of growth related signals. To date the exact mechanism of liver regeneration remains poorly understood. Toll-like receptor 4 (TLR4) acts as a sensor for immune signals and plays a critical role in host defence. It is known that lipopolysaccharide (LPS) is one of the ligands for TLR4. Binding of LPS to TLR4 leads to activation of transcription factor, nuclear factor kappa B (NF-κB) via the intracellular adaptor molecule, myeloid differentiation factor 88 (MyD88), which in turn activates the production of proinflammatory cytokines, TNF-α and IL-6. Evidence suggests that LPS/TLR4 signalling may be involved in liver regeneration following partial hepatectomy, as delayed liver regeneration and impaired cytokine responses were observed in C3H/HeJ mice, a mouse that is ...
Liver regeneration requires spatially and temporally precisely coordinated proliferation of the two major hepatic cell populations, hepatocytes and liver sinusoidal endothelial cells (LSECs), to reconstitute liver structure and function. The underlying mechanisms of this complex molecular cross-talk remain elusive. Here, we show that the expression of Angiopoietin-2 (Ang2) in LSECs is dynamically regulated after partial hepatectomy. During the early inductive phase of liver regeneration, Ang2 down-regulation leads to reduced LSEC transforming growth factor-β1 production, enabling hepatocyte proliferation by releasing an angiocrine proliferative brake. During the later angiogenic phase of liver regeneration, recovery of endothelial Ang2 expression enables regenerative angiogenesis by controlling LSEC vascular endothelial growth factor receptor 2 expression. The data establish LSECs as a dynamic rheostat of liver regeneration, spatiotemporally orchestrating hepatocyte and LSEC proliferation ...
Studies on the hyperplasia (regeneration) of the rat liver following partial hepatectomy. Changes in lipid peroxidation and general biochemical aspects
The alternative regenerative medicine approach aims to explore the post-embryonic regeneration of tissues, such as the pancreas, as a therapeutic application option for a variety of diseases. Post-embryonic regeneration of tissue applies to the liver, kidney, peripheral tissues (i.e., wound healing), and others. Many examples of tissues regeneration without soliciting stem cells exist. For example, a salamander is regenerating lost limbs without soliciting stem cell intervention. These findings give possible strategies for tissues repair in humans, beyond stem cell-based approaches. Liver regeneration following partial hepatectomy is carried out by the participation of all mature liver cell types. We demonstrated through our novel biologic approach that integrates multiple levels of somatic cellular physiology to regulate regenerative organ capacity without stem cell via a post-embryonic mechanism. This new field of research has been coined as
A delay in liver regeneration after partial hepatectomy (PHx) leads to acute liver injury, and such delays are frequently observed in aged patients. BubR1 (budding uninhibited by benzimidazole-related 1) controls chromosome mitotic segregation through the spindle assembly checkpoint, and BubR1 down-regulation promotes aging-associated phenotypes. In this study we investigated the effects of BubR1 insufficiency on liver regeneration in mice. Low-BubR1-expressing mutant (BubR1(L/L)) mice had a delayed recovery of the liver weight-to-body weight ratio and increased liver deviation enzyme levels after PHx. Microscopic observation of BubR1(L/L) mouse liver showed an increased number of necrotic hepatocytes and intercalated disc anomalies, resulting in widened inter-hepatocyte and perisinusoidal spaces, smaller hepatocytes and early-stage microvilli atrophy. Up-regulation of desmocollin-1 (DSC1) was observed in wild-type, but not BubR1(L/L), mice after PHx. In addition, knockdown of BubR1 expression caused
The liver is the only visceral organ that possesses the remarkable capacity to regenerate. The liver can regenerate after either surgical removal or after chemical injury. It is known that as little as 25% of the original liver mass can regenerate back to its full size. The process of regeneration in mammals is mainly compensatory growth because only the mass of the liver is replaced, not the shape. However, in lower species such as fish, both liver size and shape can be replaced. Liver regeneration involves replication of the liver cells, mainly hepatocytes, followed by other cells such as biliary epithelial cells and sinusoidal endothelial cells. Once cell proliferation is completed, the newly divided cells undergo restructuring, angiogenesis and reformation of extracellular matrix to complete the regeneration process. Interestingly, in most cases, liver function is only partially affected during liver regeneration. Whereas certain specialized functions such as drug metabolism decrease, many ...
Although liver regeneration occurring after partial hepatectomy (PH) is greatly reduced in aged mice, liver hyperplasia induced by xenobiotic mitogens was found to be age independent. Here, we investigated the potential utility of mitogens in stimulating liver regeneration in old mice subjected to two-third PH. Although virtually no hepatocytes entered S phase 48 h after PH, pretreatment (2 h prior to surgery) with 1,4-bis(2-(3,5-dichloropyridyloxy)benzene (TCPOBOP), a ligand of constitutive androstane receptor, induced an increase of bromodeoxyuridine incorporation and enhanced the expression of cyclin D1, cyclin A and proliferating cell nuclear antigen . Next, we investigated the potential utility of mitogens in the context of donor conditioning prior to living-related transplantation. Three days after TCPOBOP administration to intact young mice, an almost doubling of the liver mass and DNA content occurred; the regenerative response to two-third resection of the TCPOBOP-induced hyperplastic ...
Platelets are a vital part of wound healing processes. They can specifically secrete key growth factors at the site of the injury and therefore start the damaged tissues regeneration processes. In the latest study, which involved collaboration between the University Department of Surgery at the MedUni Vienna led by Patrick Starlinger and the Institute of Physiology led by Alice Assinger, scientists were able to demonstrate that the specific release of growth factors from the α granules was associated with post-operative liver regeneration.. The authors of this study demonstrated back in 2014 that serotonin stored in platelets can play a key role in post-operative liver regeneration. Serotonin is stored in the electron-dense granules (storage organelles) of platelets and is secreted after activation. As part of the platelet activation process, the contents of a second type of granule, known as the α granule, are also released. It has now been possible for the first time to prove a highly ...
To evaluate the effectiveness of omega-3 polyunsaturated fatty acid (ω-3 PUFA) administration on liver regeneration after 90% partial hepatectomy (PH) in rats. ω-3 PUFAs were intravenously injected in the ω-3 PUFA group before PH surgery. PH
In this study, we have shown that C5 is an essential component in liver regeneration following toxic injury. Mice deficient in this complement protein were unable to mount a normal regenerative response after toxic exposure to CCl4. This was demonstrated by the delayed entry of C5−/− hepatocytes into the cell cycle, the severely compromised mitotic activity detected in C5−/− livers, as well as the extensive parenchymal necrosis and fat deposition in the deficient mice that persisted until 96 h after the injury (data not shown). Reconstitution of the C5−/− mice with murine C5 resulted in a significant recovery of their regenerative phenotype, as shown by the restored hepatocyte DNA synthetic response and mitotic activity at 48 h after the toxic challenge. It should be noted that the C5−/− mice showed signs of acute necrosis and persisting degeneration until 4 days after the exposure to CCl4, a time at which the wild-type animals had completely recovered from injury. Both wild-type ...
Results siRNA-mediated knockdown of Fgfr4 severely affected liver regeneration due to impairment of hepatocyte proliferation combined with liver necrosis. Mechanistically, the proliferation defect resulted from inhibition of an Fgf15-Fgfr4-Stat3 signalling pathway, which is required for injury-induced expression of the Foxm1 transcription factor and subsequent cell cycle progression, while elevated levels of intrahepatic toxic bile acids were identified as the likely cause of the necrotic damage. Failure of liver mass restoration in Fgfr4 knockdown mice was prevented at least in part by compensatory hypertrophy of hepatocytes. Most importantly, our data revealed partially redundant functions of Fgf receptors in the liver, since knockdown of Fgfr4 in mice lacking Fgfr1 and Fgfr2 in hepatocytes caused liver failure after PH due to severe liver necrosis and a defect in regeneration.. ...
Our objective was to demonstrate the protective effect of glycine (Gly) and vitamin E (VE) on a model ofethanol-induced acute liver injury during the early phase of liver regeneration after partial hepatectomy(PH) in rats. Fifty male Wistar rats (body weight (b.w.), 240 - 280 g) were divided into four groups (n = 10,each, respectively) as follows: 1) control partial hepatectomy (PH), 70%; 2) PH + ethanol (EtOH) at 1.5g/kg b.w; 3) PH + Gly (0.6 g/kg b.w) + EtOH, and; 4) PH + VE (400 International units [IU]) + EtOH. Twentyfour h after surgery, animals were killed and liver damage and oxidative stress parameters weremeasured. Ethanol caused a decrease in serum albumin (2.27 vs 3.12 g/dL; p < 0.05), cholesterol (31.4vs 48.0 mg/dL; p < 0.05), Aspartate aminotransferase (AST, 70 vs 380 UI; p < 0.05), and alanineaminotransferase (ALT, 110 vs 170 UI; p < 0.05) in comparison with the PH control group, but thesedecreases were reverted with either Gly or VE administration. Furthermore, Gly and VE ...
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ABSTRACT CELLULAR MECHANISMS OF MAMMALIAN LIVER REGENERATION Kilangsungla Yanger Ben Z. Stanger The liver is an essential organ that aids in metabolic processes, protein synthesis and detoxification of harmful substances. As the centre for detoxification, the liver is able to compensate for this routine damage with its robust regenerative ability. All vertebrate livers, for example, can make up for tissue mass loss (via surgical excision of a portion of the liver) by replication of their differentiated cells within the remnant lobes. These differentiated cells include parenchymal cells such as the hepatocytes and biliary epithelial cells (BECs) and also non-parenchymal cells. Despite the proliferative capacity exhibited by hepatocytes, the mechanism for how the liver regenerates after toxin injuries is debated. The liver is thought to utilize facultative stem cells (FSCs) originating from the BECs, often referred to as oval cells, for regeneration following toxin-based injury. However, the notion that
The liver has an enormous capacity to regenerate, as demonstrated by the 2/3 partial hepatectomy model in rodents. In addition, the liver has a stem cell compar...
When rats were subjected to partial hepatectomy, glucosamine 6-phosphate synthase (EC 5.3.1.19) of the remaining liver underwent alterations both in activity and in molecular form. To study the molecular alterations, glucosamine 6-phosphate synthase was purified from regenerating as well as control liver and was analyzed by isoelectric focusing. Although control liver exhibited only one form of glucosamine 6-phosphate synthase with a pl of 5.0, sequential and transient appearance of three other forms, with pl values of 4.3, 4.8, and 4.5, respectively, was observed for regenerating liver within 72 hr following partial hepatectomy. Laparotomy, on the other hand, induced in the liver only the pl 4.8 form, and injection of a mixture containing triiodothyronine, amino acids, glucagon, and heparin induced only the pl 4.3 and 4.5 forms. It therefore appears that the pl 4.3 and 4.5 forms, but not the pl 4.8 form, are associated with hepatic DNA synthesis. The pl 4.8 form is induced in the liver in ...
Transfer ribonucleic acid1 is methylated after the molecule is synthesized; at least eight enzymes are involved in the transfer of methyl groups (derived from methionine). The time courses of methylation and synthesis of tRNA during rat liver regeneration have been compared in an in vivo radioisotopic study, using 6-orotic acid-14C and 3H-methyl-L-methionine as precursors in double label pulses. Liver regeneration is a synchronized system in which biochemical events of the cell cycle are separable. Transfer RNA methylation increase precedes by several hours tRNA synthesis during regeneration, although the curves overlap. A ratio of the relative rate of methylation to the relative rate of synthesis has been made; that curve positively correlates with the rise and fall of protein synthesis during regeneration. It is clear that methylation and synthesis of tRNA are only weakly coupled; changing methyl content of the tRNA "pool" resulting from differential tRNA methylase and polymerase activities ...
Lipids are the energy source used during liver regeneration. The research group, led by Dr. Albert Pol and with members from IDIBAPS, Universitat de Barcelona and Queensland University, unveils the essential role of the protein caveolin-1 in a fundamental process for liver cure after injury or transplant. Results also evidence the existence of cellular mechanisms by which excessive accumulation of lipids in the liver is a risk factor for the apparition of hepatic tumours.
Abstract: The high regenerative capacity of liver contributes to the maintenance of its size and function when injury occurs. Partial hepatectomy induces division of mature hepatocytes to maintain liver function, whereas severe injury stimulates expansion of undifferentiated hepatic precursor cells, which supply mature cells. Although several factors reportedly function in liver regeneration, the precise mechanisms underlying regeneration remain unclear. In this study, we analyzed expression of nucleostemin (NS) during development and in injured liver by using transgenic green fluorescent protein reporter (NS-GFP Tg) mice. In neonatal liver, the hepatic precursor cells that give rise to mature hepatocytes were enriched in a cell population expressing high levels of NS. In adult liver, NS was abundantly expressed in mature hepatocytes and rapidly upregulated by partial hepatectomy. Severe liver injury promoted by a diet containing 3,5-diethoxycarbonyl-1,4-dihydrocollidine induced the emergence of ...
The function of the liver is well-preserved during the aging process, although some evidence suggests that liver regeneration might be impaired with advanced age. We observed a decreased ability of the liver to restore normal volume after partial hepatectomy in elderly mice, and we identified a pathway that rescued regeneration and was triggered by serotonin. 2,5-dimethoxy-4-iodoamphetamine (DOI), a serotonin receptor agonist, reversed the age-related pseudocapillarization of old liver and improved hepatosinusoidal blood flow. After hepatectomy, the open fenestrae were associated with a restored attachment of platelets to endothelium and the initiation of a normal regenerative response, including the up-regulation of essential growth mediators and serotonin receptors. In turn, hepatocyte proliferation recovered along with regain of liver volume and animal survival. DOI operates through the release of VEGF, and its effects could be blocked with anti-VEGF antibodies both in vitro and in vivo. ...
In this work, the expression of IGFBPs in the regenerating liver was investigated. Classic reports demonstrated that IGFBP-1 is an immediate-early gene, whose expression is rapidly and dramatically increased after 70% PHx (14, 23). In our experiments this pattern was confirmed. However, serum IGFBP-1 levels appeared to be decreased during the first day of liver regeneration, returning to control values thereafter. Similarly, a decline in IGFBP-3 serum levels was observed within 24 h after PHx, without significant differences in the hepatic mRNA abundance. A rapid decrease in circulating IGFBP levels also was reported by Phillips et al. (25), who proposed that this was caused by a rapid clearance of the binding proteins from blood once the main site of production was partially removed by two-thirds hepatectomy. Moreover, as observed by Ghahary et al. (14), a decrease in circulating IGFBP-3 during liver regeneration may be caused by a drop in nutrient intake and growth hormone secretion.. Our ...
Rats of either sex as intact or partially hepatectomized (two-thirds liver removal) were injected s.c. daily for 7 days post-operatively with natural and synthetic estrogens, androgens or anabolic steroids, progesterone and adrenal cortical hormones
Scientists from TWINCORE have now published new insights on the processes involved in liver inflammation in the Journal of Hepatology: Type I interferons, on the one hand, limit viral replication and thereby help the immune cells to control the viral pathogen. On the other hand, type I interferons delay the regeneration of immune cells, which are important to adjust and maintain the immune balance within the liver during acute inflammation.
Principal Investigator:KITAMURA Tsuneo, Project Period (FY):1998 - 1999, Research Category:Grant-in-Aid for Scientific Research (C), Section:一般, Research Field:Gastroenterology
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ssion of cytokines - the process is strictly controlled, ie,these factors are usually produced only by activated cells in response to extracellular signals.Typically, this process occurs rapidly at all regulated gene expression levels, depending on the cell type and status of the cells.Thus, the cytokines are fairly large heterogeneous group of water-soluble polypeptide mediators involved in the immune response, inflammatory response, promoting proliferation, cell growth and hematopoiesis.Their impact is carried out at very low (nanomolar or peak) concentrations.Same cytokine can be produced by different cells, and the mediator, generated in one of the cell populations , may affect the function of various cell types.Different cytokines often exhibit the same biological activity.This is due to pleiotropy and multifunctional action of cytokines.. cytokine system has considerable stability thanks to the interchangeability, the duplication of mediators, their diversity, the presence of synergists ...
Principal Investigator:TAMURA Shinji, Project Period (FY):2001 - 2002, Research Category:Grant-in-Aid for Scientific Research (C), Section:一般, Research Field:Gastroenterology
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Ductular reactions (DRs) are observed in virtually all forms of human liver disease; however, the histogenesis and function of DRs in liver injury are not entirely understood. It is widely believed that DRs contain bipotential liver progenitor cells (LPCs) that serve as an emergency cell pool to regenerate both cholangiocytes and hepatocytes and may eventually give rise to hepatocellular carcinoma (HCC). Here, we used a murine model that allows highly efficient and specific lineage labeling of the biliary compartment to analyze the histogenesis of DRs and their potential contribution to liver regeneration and carcinogenesis. In multiple experimental and genetic liver injury models, biliary cells were the predominant precursors of DRs but lacked substantial capacity to produce new hepatocytes, even when liver injuries were prolonged up to 12 months. Genetic modulation of NOTCH and/or WNT/β-catenin signaling within lineage-tagged DRs impaired DR expansion but failed to redirect DRs from biliary ...
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We examined the expression of lipoprotein lipase (LPL) gene and LPL activity following a two-thirds hepatectomy and during liver regeneration. In most of the tissues studied, LPL activity increased a few hours after partial hepatectomy, but soon returned to normal levels. The greatest increase was found in the adrenal glands, plasma and liver. This increase in LPL activity in the liver could be partially due to an increase in the influx of the enzyme from extrahepatic tissues. There is, however, also a re-expression of LPL mRNA in the liver after partial hepatectomy (during the first hours). It is well known that LPL is expressed in the liver of neonatal animals, but progressively decreases during post-natal development, to reach adult levels around the time of weaning. Our results show by the first time that the remaining liver re-expresses LPL gene during the regeneration process and that the hepatocytes de-differentiate and acquire some of the neonatal characteristics. The increase in LPL ...
Our data demonstrate that the livers physiological growth response following PH involves MST1 and LATS protein modification and YAP1 activation, which is demonstrated by its nuclear localization and transcriptional activation of target genes. YAP1 involvement in liver regeneration is in agreement with others (Wu et al, 2001; Grijalva et al, 2004); however, our data fine‐tune the role of Hippo during the early hypertrophic and proliferative phases of the regenerative response. Phosphorylated MST1 and LATS1 were detected in quiescent livers; however, their phosphorylation increased at early time points after PH. Although this may appear contradictory to a proliferative response, this increase occurs during the hypertrophy phase of regeneration before the onset of hepatocyte proliferation (Miyaoka et al, 2010). As the hypertrophy phase transitions into the proliferative phase, levels of p‐MST and p‐LATS1 decrease coinciding with Ki67 immunostaining and YAP1 activation. We did not observe ...
Hepatocellular carcinoma (HCC) is the most commonly diagnosed form of liver cancer with high morbidity and mortality. Copy number variation analysis (CNV) of human HCC revealed that over 50% of the HCC samples examined had CNV in the gene leukocyte specific protein-1 (LSP1). LSP1, a F-actin binding protein, is expressed in hematopoietic cells and interacts with Kinase Suppressor of Ras (KSR), a scaffold for the ERK/MAPK pathway. The expression of LSP1 in liver and its role in normal hepatocellular function and carcinogenesis remains unknown. Therefore, LSP1 mRNA and protein levels were analyzed in normal hepatocytes in culture, rat liver following partial hepatectomy (PHx), and hepatoma cell lines. In culture and after PHx, LSP1 increased after the termination of hepatocyte proliferation and migration. To investigate LSP1 function in HCC, shRNA was utilized to stably knock down LSP1 expression in the JM1 rat hepatoma cell line. Loss of LSP1 in JM1 cells resulted in dramatic upregulation of ...
TY - JOUR. T1 - An inducible autocrine cascade regulates rat hepatocyte proliferation and apoptosis responses to tumor necrosis factor-α. AU - Cosgrove, Benjamin D.. AU - Cheng, Connie. AU - Pritchard, Justin R.. AU - Stolz, Donna B.. AU - Lauffenburger, Douglas A.. AU - Griffith, Linda G.. PY - 2008/7/1. Y1 - 2008/7/1. N2 - Tumor necrosis factor-α (TNF) is an inflammatory cytokine that induces context-dependent proliferation, survival, and apoptosis responses in hepatocytes. TNF stimulates and enhances growth factor-mediated hepatocyte proliferation and survival following partial hepatectomy, but also acts in concert with other inflammatory cytokines of the innate immune response during viral infection to induce apoptosis in hepatocytes. In other epithelial cell types, TNF has recently been shown to stimulate autocrine release of transforming growth factor-α (TGF-α) and interleukin-1 (IL-1) family ligands. Here, we examine the role of these autocrine ligands in modulating TNF-induced ...
There are other substances which help the healing nerve sheath fixing myelin nerve fiber. Music and falling in love and positive influence on the regeneration and recovery of neurons.. Liver regeneration. Glycyrrhizin is a compound found in licorice root and which, according to one study provided an excellent regeneration of the stimulant in animals in which it is surgically removed on a part of the liver.. Other substances that help liver regeneration are: carvacrol (from oil of oregano), curcumin (root of the plant Curcuma), ginseng, Korean artichoke, vitamin E (tofu, spinach, almonds, sunflower seeds, avocado, shrimp, fish, olive oil, broccoli , pumpkins and squash).. Regeneration of beta cells. Beta cells in the pancreas produces insulin. The following compounds was successfully experimented to help diabetics: silver svilenica, black cumin, vitamin D (fish, caviar, eggs, cheese), curcumin (root turmeric), arginine (red meat, soy, eggs, seafood, sesame) , avocado, bitter melon, chard, corn ...
Type beta transforming growth factor (TGF-beta), a factor produced by many cell types, is a potent inhibitor of hepatocyte DNA synthesis in vitro. To determine whether TGF-beta can influence hepatocyte proliferation in vivo, its effects were examined on the regenerative response of liver to partial hepatectomy (PH) in the rat. Porcine platelet-derived TGF-beta 1 (0.5 micrograms), administered intravenously at the time of PH and 11 hr later, reduced the fraction of hepatocytes engaged in DNA synthesis 22 hr after PH by 67% and inhibited the rate of hepatic [3H]thymidine incorporation by 50%. TGF-beta 2 produced a similar effect. A single dose of 0.5 micrograms of TGF-beta 1 given 11 hr after PH reduced liver [3H]thymidine incorporation by 32%; 4.5 micrograms of TGF-beta 1 or TGF-beta 2 inhibited DNA synthesis by 88% and the labeling index by 86%. Although sensitive to TGF-beta administered 11 hr after PH, late in the G1 phase of the cell cycle, a single dose of 0.5 micrograms given at the time of ...
Liver diseases are known to affect the function of remote organs. The aim of the present study was to investigate the effects of Pringle maneuver, which results in hepatic ischemia-reperfusion (IR) injury, and partial hepatectomy (Hx) on the pharmacokinetics and brain distribution of sodium fluorescein (FL), which is a widely used marker of blood-brain barrier (BBB) permeability. Rats were subjected to Pringle maneuver (total hepatic ischemia) for 20 min with (HxIR) or without (IR) 70% hepatectomy. Sham-operated animals underwent laparotomy only. After 15 min or 8 h of reperfusion, a single 25-mg/kg dose of FL was injected intravenously and serial (0-30 min) blood and bile and terminal brain samples were collected. Total and free (ultrafiltration) plasma, total brain homogenate, and bile concentrations of FL and/or its glucuronidated metabolite (FL-Glu) were determined by HPLC. Both IR and HxIR caused significant reductions in the biliary excretions of FL and FL-Glu, resulting in significant increases
The enormous regenerative capacity of the liver after partial hepatectomy or chemical injury is well known. In rodents, liver weight returns to normal within a few weeks even after loss of up to two-thirds of total liver mass (Fausto and Webber, 1994). Remarkable regenerative potential is also retained in hematopoiesis. Hematopoietic stem cells (HSCs)* certainly exist in bone marrow where they self-renew and differentiate along all hematopoietic lineages. Sophisticated isolation methods have recently identified a highly probable HSC candidate; a single such cell can reconstitute bone marrow (Osawa et al., 1996). By analogy with hematopoiesis, liver regeneration can be regarded as mediated by proliferation and differentiation of hepatic stem cells. However, it remains unclear how the liver is regenerated and what cells are involved in such regeneration. Overturf et al. (1997) inferred from serial transplantation studies the presence in adult mouse liver of cells capable of dividing more than 60 ...
Acute liver failure caused by viral hepatitis or toxic damage involves both apoptotic and necrotic pathways. IGF binding protein-1 (IGFBP-1), a hepatocyte-derived secreted protein, is required for normal liver regeneration. To determine whether IGFBP-1 could prevent liver injury that entails direct stimulation of hepatocyte apoptosis, IGFBP-1-/- mice, IGFBP-1+/+ mice, and mice pretreated with Abs against IGFBP-1 were treated with a normally sublethal dose of Fas agonist. IGFBP-1 deficiency was associated with massive hepatocyte apoptosis and caspase activation within 3 hours of Fas agonist treatment, which could be corrected by pretreatment with IGFBP-1. IGFBP-1-deficient livers had enhanced signaling via the integrin receptor at early times (0.5 to 1 hour) after Fas agonist treatment accompanied by elevated activated matrix metalloproteinase-9 (MMP-9), a known target of fibronectin signaling and activator of TGF-β. Within 3 hours of Fas agonist treatment, elevated expression of active ...
Background: The zinc finger transcription factor Egr-1 (Early growth response 1) is central to several growth factors and represents an important activator of target genes not only involved in physiological processes like embryogenesis and neonatal development, but also in a variety of pathophysiological processes, for example atherosclerosis or cancer. Current options to investigate its transcription and activation in vivo are end-point measurements that do not provide insights into dynamic changes in the living organism. Results: We developed a transgenic mouse (Egr-1-luc) in which the luciferase reporter gene is under the control of the murine Egr-1 promoter providing a versatile tool to study the time course of Egr-1 activation in vivo. In neonatal mice, bioluminescence imaging revealed a high Egr-1 promoter activity reaching basal levels three weeks after birth with activity at snout, ears and paws. Using a model of partial hepatectomy we could show that Egr-1 promoter activity and Egr-1 ...
In many cases, chronic or acute damage to the liver, as a direct result of hepatitis infection or poisoning, can lead to the loss of the organs capacity to self-renew. For those affected, this can be life-threatening: "In such instances, patients cannot avoid organ transplantation," explains Professor Lars Zender, liver specialist at Tübingen University Hospital, who was conducting research at the HZI and Hannover Medical School until 2012. "Each year, over a million people die from chronic or acute liver failure and many patients do not survive the often extensive waiting times for a transplant organ.". Zender and his colleagues at the participating research sites have identified a new potential thera-peutic target: a protein kinase called MKK4. Inhibition of the murine MKK4 gene increases the livers potential for regeneration considerably. The result: noticeable improvements in the animals survival rate following acute or chronic liver failure. To a large extent, the different technologies ...
Changes in binding of dexamethasone (9α-fluoro-11β, 17α,21-trihydroxy-16α-methylpregna-1,4-diene-3,20-dione) to its receptors in regenerating rat liver after 70% hepatectomy were examined. Specific receptors for dexamethasone in the liver remnants of adrenalectomized rats decreased significantly during the period of DNA synthesis after 70% hepatectomy; then, they increased to above the control values between Days 4 and 7 after partial hepatectomy and subsequently returned to the control values. During the period of DNA synthesis, decreased binding was observed in partially hepatectomized rats with or without adrenals, but later enhanced binding was not prominent in rats with adrenals.. ...
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Diagnosis and treatment of cancer of the bile duct with partial hepatectomy (costs for program #275070) ✔ Klinik Im Park ✔ Department of General and Abdominal Surgery ✔ BookingHealth.com
Heard a myth that if you stop drinking any alcohol for 5 weeks straight, your liver will be able to "heal" any prior alcohol-related damage (assuming you arent an alcoholic or have other permanent liver problems). Seems a bit far- fetched and would like your opinion. Thanks ...
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Stem Cells International is a peer-reviewed, Open Access journal that publishes original research articles, review articles, and clinical studies in all areas of stem cell biology and applications. The journal will consider basic, translational, and clinical research, including animal models and clinical trials.
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Background Hepatic resection is not applicable to the majority ofhepatocellular carcinoma (HCC) patients due to insufficient liverfunction reserve. Cardiotrophin-1 (CT-1), a member of the inter-leukin-6 family, has demonstrated protective and pro-proliferativeeffects in the myocytes and hepatocytes.Aim The present study aimed to investigate the potential role ofCT-1 in rescuing marginal cirrhotic liver remnant in a rat orthotopicHCC model.Materials and Methods Liver cirrhosis was induced by subcuta-neous injection of CCL4 for 8 weeks. The rat orthotopic HCC model was generated by injecting HCC cells into the left lobe of the liver.Animals received the following treatments: 1) hepatectomy only, n =6; 2) CT-1 (2 µg/kg) intraportal vein injection (i.pv) right after hepa-tectomy, n = 6; 3) CT-1 (2 µg/kg) i.pv right after hepatectomy, and 1µg/kg intraperitoneal injection (i.p) 24 hr after hepatectomy, n = 6; 4)CT-1 (2 µg/kg) i.p 24 hr before hepatectomy, n = 6; 5) CT-1 (2 µg/kg)i.p 24 hr before ...
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