Maternal exposure to carbon black nanoparticle increases collagen type VIII expression in the kidney of offspring.
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The potential health risks of inhaling nanomaterials are of great concern because of their high specific activity and their unique property of translocation. Earlier studies showed that exposure to nanoparticles through the airway affects both respiratory and extrapulmonary organs. When pregnant mice were exposed to nanoparticles, the respiratory system, the central nervous system and the reproductive system of their offspring were affected. The aim of this study was to assess the effect of maternal exposure to nanoparticles on the offspring, particularly on the kidney. Pregnant ICR mice were exposed to a total of 100 microg of carbon black nanoparticle on the fifth and the ninth days of pregnancy. Samples of blood and kidney tissue were collected from 3-week-old and 12-week-old male offspring mice. Collagen expression was examined by quantitative RT-PCR and immunohistochemistry. Serum levels of creatinine and blood urea nitrogen were examined. Exposure of pregnant ICR mice to carbon black resulted in increased expression of Collagen, type VIII, a1 (Col8a1) in the tubular cells in the kidney of 12-week-old offspring mice but not in 3-week-old ones. The levels of serum creatinine and blood urea nitrogen, indices of renal function, were not different between the groups. These observations were similar to those of tubulointerstitial fibrosis in diabetic nephropathy. These results suggest that maternal exposure to carbon black nanoparticle induces renal abnormalities similar to tubulointerstitial fibrosis in diabetic nephropathy are induced in the kidney of offspring. (+info)
An alpha 2 collagen VIII transgenic knock-in mouse model of Fuchs endothelial corneal dystrophy shows early endothelial cell unfolded protein response and apoptosis.
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Mice with an induced mutation in collagen 8A2 develop larger eyes and are resistant to retinal ganglion cell damage in an experimental glaucoma model.
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PURPOSE: To study susceptibility to glaucoma injury as it may be affected by mutations in ocular connective tissue components. METHODS: Mice homozygous for an N-ethyl-N-nitrosourea induced G257D exchange (Gly to Asp) missense mutation (Aca23) in their collagen 8A2 gene were studied to measure intraocular pressure (IOP), axial length and width, number of retinal ganglion cells (RGC), and inflation responses. Three month old homozygous Aca23 mutant and wild type (WT) mice had 6 weeks exposure to elevated IOP induced by polystyrene microbead injection. Additional Aca23 and matched controls were studied at ages of 10 and 18 months. RESULTS: Aca23 mice had no significant difference from WT in IOP level, and in both strains IOP rose with age. In multivariable models, axial length and width were significantly larger in Aca23 than WT, became larger with age, and were larger after exposure to glaucoma (n=227 mice). From inflation test data, the estimates of scleral stress resultants in Aca23 mice were similar to age-matched and younger WT C57BL/6 (B6) mice, while the strain estimates for Aca23 were significantly less than those for either WT group in the mid-sclera and in some of the more anterior scleral measures (p<0.001; n=29, 22, 20 eyes in Aca23, older WT, younger WT, respectively). With chronic IOP elevation, Aca23 eyes increased 9% in length and 7% in width, compared to untreated fellow eyes (p<0.05, <0.01). With similar elevated IOP exposure, WT eyes enlarged proportionately twice as much as Aca23, increasing in length by 18% and in nasal-temporal width by 13% (both p<0.001, Mann-Whitney test). In 4 month old control optic nerves, mean RGC axon number was not different in Aca23 and WT (46,905+/-7,592, 43,628+/-11,162, respectively; p=0.43, Mann-Whitney test, n=37 and 29). With chronic glaucoma, Aca23 mice had a mean axon loss of only 0.57+/-17%, while WT mice lost 21+/-31% (median loss: 1% versus 10%, n=37, 29, respectively; p=0.001; multivariable model adjusting for positive integral IOP exposure). CONCLUSIONS: The Aca23 mutation in collagen 8alpha2 is the first gene defect found to alter susceptibility to experimental glaucoma, reducing RGC loss possibly due to differences in mechanical behavior of the sclera. Detailed study of the specific changes in scleral connective tissue composition and responses to chronic IOP elevation in this strain could produce new therapeutic targets for RGC neuroprotection. (+info)
Collagen VIII influences epithelial phenotypic changes in experimental diabetic nephropathy.
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L450W and Q455K Col8a2 knock-in mouse models of Fuchs endothelial corneal dystrophy show distinct phenotypes and evidence for altered autophagy.
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