Injury vascular cyclin dependent kinase inhibitor. Medical search. Frequent questions

EC-Foxp1 regulates matrix metalloproteinase-9/cyclin dependent kinase inhibitor 1B signaling pathway to control injury induced neointimal formation. (bvsalud.org)

Expression of the promoter is shown to be induce by phorbol esters and cyclic-AMP-dependent protein kinase signaling. (wikipedia.org)
The PFKFB3 inducible isoform has higher '2-Kase' (kinase) activity than other isoforms, due to phosphorylation of Ser-460 by PKA or AMP-dependent protein kinase. (wikipedia.org)
They further link to the activation of protein kinase C- (PKC-) induced generation of reactive oxygen species (ROS) [ 6 , 7 ], which further mediates the activation of downstream transcription factor nuclear factor kappa-light-chain enhancer of activated B cells (NF- κ B). Thus, the main treatments of DN refer to modulate glycemic and blood pressure through insulin and RAS inhibitors. (hindawi.com)
CDK4 is a member of the Ser/Thr protein kinase family. (thermofisher.com)
It is a catalytic subunit of the protein kinase complex that is important for cell cycle G1 phase progression. (thermofisher.com)
The overexpression of miRNA‑375 significantly increased caspase‑3 and caspase‑9 activities, induced B‑cell lymphoma 2 (Bcl‑2)/Bcl‑2‑associated X protein, tumor protein 53 and cyclin‑dependent kinase inhibitor 1 protein expression and suppressed cyclin D1 and survivin protein expression in HPV‑18(+) cervical cancer cells. (spandidos-publications.com)
In addition, numerous important cellular proteins, such as B-cell lymphoma-2 homologous antagonist/killer, Myc proto-oncogene protein, cyclin-dependent kinase inhibitor 1B, DNA replication licensing factor MCM-7, retinoblastoma 1 and Annexin A1, are degenerated through the UBE3A-mediated ubiquitin proteasome pathway ( 7 ). (spandidos-publications.com)
However, recent studies have suggested that BRAFi/MEKi and ERK1/2i resistance can arise through activation of a parallel signalling pathway leading to activation of ERK5, an unusual protein kinase that contains both a kinase domain and a transcriptional transactivation domain. (babraham.ac.uk)
Receptor-interacting protein kinase 1 (RIPK1), a key molecule mediating necroptosis and regulated by transforming growth factor β-activated kinase 1 (TAK1), was reported to be associated with cognitive impairment in several neurodegenerative diseases. (imperial.ac.uk)
Because FGF2 and P2 purinergic receptors are coupled to extracellular signal regulated protein kinase (ERK), a key member of a signaling cascade that regulates proliferation, we also investigated the role of ERK in regulating cyclin expression induced by FGF2 and ATP. (sagepub.com)
The mitogen-activated protein (MAP) kinase cascade can either stimulate or inhibit DNA synthesis in primary cultures of rat hepatocytes depending upon whether its activation is acute/phasic or chronic. (sagepub.com)

Although the senescent cells remain viable, they show typical changes with enlarged and flattened cell bodies, apoptosis resistance, increased activity of senescence-associated β -galactosidase (SA- β -gal), and upregulation of cyclin-dependent kinase (CDK) inhibitors including p16 INK4A , ARF proteins, and p21 [ 13 - 16 ]. (hindawi.com)
The activity of this kinase is restricted to the G1-S phase, which is controlled by the regulatory subunits D-type cyclins and CDK inhibitor p16(INK4a). (thermofisher.com)
Mutations in this gene as well as in its related proteins including D-type cyclins, p16(INK4a) and Rb were all found to be associated with tumorigenesis of a variety of cancers. (thermofisher.com)
SnCs exhibit irreversible growth arrest accompanied by increased expression of cyclin-dependent kinase inhibitors (CDKi) such as p16 INK4a , and p21 Cip1 , accumulation of DNA damages, and secretion of diverse bioactive molecules known as the senescence-associated secretory phenotype (SASP). (aging-us.com)

Over 500 products have been investigated for neuroprotective effects including those from the categories of free radical scavengers, anti-excitotoxic agents, apoptosis (programmed cell death) inhibitors, anti-inflammatory agents, neurotrophic factors, metal ion chelators, ion channel modulators, and gene therapy. (researchandmarkets.com)

This kinase was shown to be responsible for the phosphorylation of retinoblastoma gene product (Rb). (thermofisher.com)
This has led to the development of a range of ERK1/2 inhibitors (ERKi) that either inhibit kinase catalytic activity (catERKi) or additionally prevent the activating pT-E-pY dual phosphorylation of ERK1/2 by MEK1/2 (dual-mechanism or dmERKi). (babraham.ac.uk)
Sema 3A mediated retraction appears to be related to its binding to Npn 1 and Plxn A2 receptors, thus activating the downstream Fyn tyrosine kinase pathway that promotes the threonine-serine kinase cyclin-dependent kinase 5, CDK5, phosphorylation at the Tyr15 residue and the CDK5 processing to generate the active fragment p35. (biomedcentral.com)
TGF-β1 acts predominantly through phosphorylation of the C-terminal MH2 domains of SMAD2 and SMAD3 via activin receptor-like kinase 5 (ALK5), of which activity is located at the C-terminal part of TGFBR1. (springer.com)

HDAC inhibition resulted in a transcriptional and posttranscriptional regulation of the cyclin-dependent kinase inhibitors p21(Cip1) and p27(Kip). (cret-signal.com)

The occurrence and development of PH is closely related to pulmonary vascular remodeling and abnormal function. (imrpress.com)
Pulmonary hypertension (PH) is a chronic and progressive disease characterized by enhanced pulmonary vascular resistance and elevated pulmonary artery pressure resulted from pulmonary vascular remodeling and vasoconstriction [ 1 ]. (imrpress.com)
Considerable evidence from basic and clinical experiment has demonstrated that pulmonary vascular remodeling caused by impairment of endothelial cells (ECs), pulmonary artery spasm, adhesion and mligration of inflammatory cells to the pulmonary artery wall, adventitial fibrosis, intimal occlusive fibrosis, and fibrinoid necrosis are typical pathological features in many forms of PH. (imrpress.com)
Pulmonary vascular remodeling is the result, and, likely, contributes to increased pulmonary vascular pressures by increasing pulmonary vascular resistance [ 6 , 7 ]. (imrpress.com)
However, the mechanism of pulmonary vascular remodeling has not been fully elucidated, there is still a lack of effective drugs to prevent and reverse pulmonary vascular remodeling. (imrpress.com)
Intercellular communication, a key process in pulmonary vascular remodeling, is originally believed to be achieved by either direct cell-to-cell contact or paracrine effects. (imrpress.com)
Platelet-activating factor stimulates ovine foetal pulmonary vascular smooth muscle cell proliferation: role of nuclear factor-kappa B and cyclin-dependent kinases. (anbapharma.com)

Atherosclerosis is a chronic vascular inflammatory disease associated to oxidative stress and endothelial dysfunction. (hindawi.com)
n\nConclusion-These findings identify HDAC as a critical component of a transcriptional cascade regulating SMC proliferation and suggest that HDAC might play a pivotal role in the development of proliferative vascular diseases, including atherosclerosis and in-stent restenosis. (cret-signal.com)

EC-Foxp1 deletion mice displayed the increased neointimal formation through elevation of vascular smooth muscle cell proliferation and migration, and the reduction of EC proliferation hence reendothelialization after injury. (bvsalud.org)
EC-Foxp1 paracrine regulated vascular smooth muscle cell proliferation and migration via targeting matrix metalloproteinase-9. (bvsalud.org)
Notably, the knockdown of HSP70 by HSP70 siRNA apparently abrogates the stimulatory effect of let-7c inhibitor on heat-denatured fibroblasts proliferation and migration. (molcells.org)

While developmental senescence and acute senescence may positively contribute to the fine-tuning of embryogenesis and injury repair, chronic senescence, when unresolved promptly, plays a crucial role in kidney fibrogenesis and CKD progression. (frontiersin.org)
Senescent cells (SnCs) have been described to accumulate in osteoarthritis (OA) joint tissues in response to injury, thereby participating in OA development and progression. (aging-us.com)
Indeed, senescent cells (SnCs) are described to accumulate in joint tissues in response to injury and during aging, thereby participating in its development and progression [ 8 - 10 ]. (aging-us.com)

Transcription factor Gata6 has been reported to regulate vascular endothelial cell activation and inflammation in vitro. (bvsalud.org)
Transgenic FOXM1 expression or in vivo endothelium-targeted nanoparticle delivery of the FOXM1 gene driven by an endothelial cell (EC)-specific promoter reactivated endothelial regeneration, normalized vascular repair and resolution of inflammation, and promoted survival in aged mice after sepsis challenge. (bvsalud.org)

The main groups include sodium channel blockers, calcium current inhibitors, gamma-aminobutyric acid (GABA) enhancers, glutamate blockers, carbonic anhydrase inhibitors, hormones, and drugs with unknown mechanisms of action (see the image below). (medscape.com)

Endothelial dysfunction results in chronic vascular inflammation, which is critical for the development of atherosclerotic diseases. (bvsalud.org)
Cardiovascular (CV) risk factors such as hypercholesterolemia, hyperglycaemia, obesity, hypertension, smoking, and aging promote vascular inflammation and endothelial activation [ 7 - 9 ]. (hindawi.com)

5: de Oliveira SI, Andrade LN, Onuchic AC, Nonogaki S, Fernandes PD, Pinheiro MC, Rohde CB, Chammas R, Jancar S. Platelet-activating factor receptor (PAF-R)-dependent pathways control tumour growth and tumour response to chemotherapy. (anbapharma.com)
By contrast, other inhibitions of growth-signals like those associated with receptor tyrosine kinases are referred to as targeted therapy. (worldsbest.rehab)
P2 receptor agonist studies revealed that UTP enhanced FGF2-induced cyclin expression and mitogenesis whereas 2-methylthioADP was ineffective. (sagepub.com)

This inhibition takes place mainly by interactions and stabilization of IB, and interactions together with the IB kinases. (pka-signal.com)
Similarly, marked modifications occur in the larger phosphoprotein clusters involving cytoskeleton and neuronal structures, membrane stabilization, and kinase regulation in the late elderly.Present findings may increase understanding of human brain proteostasis modifications in the elderly in the subpopulation of individuals not having AD neuropathological change and any other neurodegenerative change in any telencephalon region. (ibecbarcelona.eu)

Background The endothelium is essential for maintaining vascular physiological homeostasis and the endothelial injury leads to the neointimal hyperplasia because of the excessive proliferation of vascular smooth muscle cells. (bvsalud.org)
Methods and Results The wire injury femoral artery neointimal hyperplasia model was performed in Foxp1 EC-specific loss-of-function and gain-of-function mice. (bvsalud.org)
Delivery of cyclin dependent kinase inhibitor 1B-siRNA to ECs using RGD (Arg-Gly-Asp)-peptide magnetic nanoparticle normalized the EC-Foxp1 deletion-mediated impaired EC repair and attenuated the neointimal formation. (bvsalud.org)
Objective-Proliferation of smooth muscle cells (SMC) in response to vascular injury is central to neointimal CX-6258 vascular remodeling. (cret-signal.com)

Cytosine monophosphate kinase 2 (Cmpk2) was identified as a direct target gene of GATA6 and EC-GATA6 deletion decreased monocyte adherence, migration and pro-inflammatory macrophage foam cell formation through regulation of the CMPK2-Nlrp3 pathway. (bvsalud.org)
PFKFB3 is a gene that encodes the 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 enzyme in humans. (wikipedia.org)
Our findings demonstrate that acquisition of MEK inhibitor resistance often occurs through gene amplification and can be suppressed by impeding cell cycle entry in drug. (babraham.ac.uk)

Our results suggest that ERKi, including current clinical candidates, act as 'kinase degraders', driving the proteasome-dependent turnover of their major target, ERK2. (babraham.ac.uk)
These resistance mechanisms frequently involve reinstatement of ERK1/2 signalling and BRAFi are now deployed in combination with one of three approved MEK1/2 inhibitors (MEKi) to provide more durable, but still transient, clinical responses. (babraham.ac.uk)

We found that ATP potentiated the ability of FGF2 to stimulate expression of cyclin D1, a regulator of cell cycle entry, as well as cyclin A, a regulator of DNA replication. (sagepub.com)
These findings suggest that signaling by P2Y receptors, most likely of the purine/pyrimidine subtype, enhance the ability of FGF2 to stimulate entry into a new cell cycle, as well as DNA replication, by an ERK-dependent mechanism, whereas signaling by P2X receptors, possibly the P2X7 subtype, inhibits FGF2-induced mitogenesis in astrocytes. (sagepub.com)

Among the many risk factors for OA, including obesity, female gender, history of traumatic joint injury, and genetic predisposition, aging is the primary determinant [ 4 ]. (aging-us.com)
ERKi treatment of cells drives the poly-ubiquitylation and proteasome-dependent turnover of ERK2 and pharmacological or genetic inhibition of Cullin-RING E3 ligases prevents this. (babraham.ac.uk)
Genetic lineage tracing study showed that endothelial regeneration after sepsis-induced vascular injury was mediated by lung resident endothelial proliferation in young adult mice, whereas this intrinsic regenerative program was impaired in aged mice. (bvsalud.org)

Along with the kidney injury, diabetic patients often suffer from multiple complications, such as retinopathy, neuropathy, and cardiovascular diseases. (hindawi.com)
After adjusting for the other major risk factors for CVD, one study found the odds of vascular diseases increased with every decade of life, demonstrating a strong increase in peripheral arterial disease (PAD), carotid artery stenosis, and abdominal aortic aneurysm (AAA) with advanced age [ 4 ] . (oaepublish.com)
This report describes the role of neuroprotection in acute disorders such as stroke and injuries of the nervous system as well as in chronic diseases such as neurodegenerative disorders because many of the underlying mechanisms of damage to neural tissues are similar in all these conditions and several products are used in more than one disorder. (researchandmarkets.com)

however, the physiological role of histone acetylation for proliferative vascular disease remains elusive. (cret-signal.com)

Conclusions Our study reveals that targeting EC-Foxp1-matrix metalloproteinase-9/cyclin dependent kinase inhibitor 1B pathway might provide future novel therapeutic interventions for restenosis. (bvsalud.org)

Also, EC-Foxp1 deletion impaired EC repair through reduction of EC proliferation via increasing cyclin dependent kinase inhibitor 1B expression. (bvsalud.org)
cyclin D1 mRNA expression and cyclin D1 promoter activity. (cret-signal.com)
Finally, we provide evidence that these observations are applicable in vivo by demonstrating that HDAC inhibition decreased neointima formation and expression of cyclin D1 in a murine model of vascular injury. (cret-signal.com)
Several hallmarks of cellular senescence, such as cell cycle arrest, expression of cyclin-dependent kinase inhibitors, DNA damages, and senescence-associated secretory profile were evaluated. (aging-us.com)
In summary, we observed sustained Inhibitors,Modulators,Libraries IEG expression despite an enrichment of DUSP relatives members in the EMT clusters. (pka-signal.com)
TAK1 inhibition exacerbated surgery-induced pRIPK1 expression, neuroinflammation and cognitive dysfunction in young rats, and this effect was reversed by a RIPK1 inhibitor. (imperial.ac.uk)
To determine whether the potentiating effect of extracellular ATP involves cell cycle control mechanisms, we have measured the expression of cyclins that are induced in different phases of the cell cycle in primary cultures of rat cortical astrocytes. (sagepub.com)
We found that the potentiating effect of ATP on cyclin expression was significantly reduced by U0126, an inhibitor of MEK, the upstream activator of ERK. (sagepub.com)

Innate or acquired resistance to small molecule BRAF or MEK1/2 inhibitors (BRAFi or MEKi) typically arises through mechanisms that sustain or reinstate ERK1/2 activation. (babraham.ac.uk)

The 50 most influential original articles in vascular surgery during the last 25 years. (vumc.org)
The young rats were treated with the TAK1 inhibitor takinib or the RIPK1 inhibitor necrostatin-1 (Nec-1) before surgery, and old rats received adeno-associated virus (AAV)-TAK1 before surgery. (imperial.ac.uk)

In the vasculature specifically, aging contributes to decreasing vascular compliance. (oaepublish.com)

The atherosclerotic process is accelerated by a myriad of factors, such as the release of inflammatory chemokines and cytokines, the generation of reactive oxygen species (ROS), growth factors, and the proliferation of vascular smooth muscle cells. (hindawi.com)
In addition, treatment with the FDA-approved DNA demethylating agent decitabine was sufficient to reactivate FoxM1-dependent endothelial regeneration in aged mice, reverse aging-impaired resolution of inflammatory injury, and promote survival. (bvsalud.org)

Type 1 diabetes mellitus (insulin-dependent diabetes) is characterized by hyperglycemia caused by an insulin deficiency. (researchgate.net)
In this study, we investigated whether DIM could improve insulin-dependent diabetes and nephropathy in streptozotocin (STZ)-induced diabetic mice. (researchgate.net)

10: Souza LJ, Shio MT, Molan NA, Machado MC, Jancar S. Acute pancreatitis affects non-parenchymal liver cells by a mechanism dependent on platelet-activating factor. (anbapharma.com)

In COVID-19 lung autopsy samples, FOXM1 was not induced in vascular ECs of elderly patients in their 80s, in contrast with middle-aged patients (aged 50 to 60 years). (bvsalud.org)
Thus, reactivation of FoxM1-mediated endothelial regeneration and vascular repair may represent a potential therapy for elderly patients with ARDS. (bvsalud.org)

Controlling these factors reduces the risk of acute vascular complications and death from CVD [ 1 , 7 ]. (hindawi.com)

However, the regulatory mechanisms of HPV infection and consequent immune escape reaction, persistent infection and cell proliferation and the regulatory mechanisms of vascular proliferation are poorly understood and require additional investigation ( 4 ). (spandidos-publications.com)

Increasing evidence indicates that senescent cells could be a promising new target for therapeutic intervention known as senotherapy, which includes depleting senescent cells, modulating SASP and restoration of senescence inhibitors. (frontiersin.org)
Figure 2: Telomere-dependent senescence. (nature.com)

When used in vivo in a mouse model of ischaemic stroke, PFKFB3 inhibitor alleviates motor discoordination and brain infarct injury The Warburg effect, proposed by Otto Warbug in 1956, describes the upregulation of glycolysis in most cancer cells, even in the presence of oxygen. (wikipedia.org)

Here, using pharmacological inhibitors, we investigate a role for V-ATPase during non-canonical autophagy. (babraham.ac.uk)
Here, we investigate amplification events that underlie resistance to the MEK inhibitor selumetinib (AZD6244/ARRY-142886) in COLO205 cells, a well-characterized model for reproducible emergence of drug resistance, and show that amplifications acquired are the primary cause of resistance. (babraham.ac.uk)

The high '2-Kase' activity of PFKFB3 is also due to the lack of a specific Ser that is phosphorylated in the other PFKFB isoforms to decrease kinase activity. (wikipedia.org)

Here, we demonstrated that persistent lung injury and high mortality in aged mice after sepsis challenge were attributable to impaired endothelial regeneration and vascular repair. (bvsalud.org)

Interactions between P2Y, P2X and polypeptide growth factor signaling pathways may have important implications for CNS development as well as injury and repair. (sagepub.com)

Vascular endothelial cells, as a monolayer in direct contact with the flowing blood, bear the most of the wall shear stresses and have important homeostatic functions in response to stress [16] . (plos.org)

We employed TNF as being a proinflammatory cytokine to en hance TGFB induced EMT in our model system, and we discover that genes that propagate TNF signaling are upregulated and strongly enriched in GC16 and GC19. (pka-signal.com)
11: Riccio M, Pangrazi PP, Campodonico A, Scalise A, Marchesini A, Talevi D, Carboni A, Bertani C, Bertani A, Mazzanti L. Combined use of WEB2170 and HBO therapy can reduce ischemia and reperfusion injury to the skeletal muscle in a rabbit model. (anbapharma.com)

En face co-immunostaining of the mouse aortic arch revealed a low level of PDCD4 in endothelial cells undergoing pulsatile shear stress. (plos.org)

Anatomy10

Organisms8

Diseases22

Chemicals and Drugs157

Analytical, Diagnostic and Therapeutic Techniques and Equipment13

Phenomena and Processes42

Disciplines and Occupations1

Information Science5

Health Care2

Signaling pathway1

Protein11

INK4A4

Apoptosis1

Phosphorylation4

Cip11

Pulmonary vascular7

Atherosclerosis2

Proliferation and migration3

Progression3

Endothelial cell2

Blockers1

Inflammation2

Receptor3

Stabilization2

Neointimal4

Gene3

Clinical2

Replication2

Genetic3

Diseases3

Physiological1

Targeting1

Expression8

Molecule1

Surgery2

Contributes1

Inflammatory2

Insulin2

Mechanism1

Patients2

Complications1

Regulatory1

Senescence2

Stroke1

Investigate2

Activity1

Mice1

Development1

Response1

Model2

Cells1