| First Author | Roberts-Pilgrim AM | Year | 2011 |
| Journal | Mol Genet Metab | Volume | 104 |
| Issue | 3 | Pages | 373-82 |
| PubMed ID | 21855382 | Mgi Jnum | J:178244 |
| Mgi Id | MGI:5297753 | Doi | 10.1016/j.ymgme.2011.07.025 |
| Citation | Roberts-Pilgrim AM, et al. (2011) Deficient degradation of homotrimeric type I collagen, alpha1(I)3 glomerulopathy in oim mice. Mol Genet Metab 104(3):373-82 |
| abstractText | Col1a2-deficient (oim) mice synthesize homotrimeric type I collagen due to nonfunctional proalpha2(I) collagen chains. Our previous studies revealed a postnatal, progressive type I collagen glomerulopathy in this mouse model, but the mechanism of the sclerotic collagen accumulation within the renal mesangium remains unclear. The recent demonstration of the resistance of homotrimeric type I collagen to cleavage by matrix metalloproteinases (MMPs), led us to investigate the role of MMP-resistance in the glomerulosclerosis of Col1a2-deficient mice. We measured the pre- and post-translational expression of type I collagen and MMPs in glomeruli from heterozygous and homozygous animals. Both the heterotrimeric and homotrimeric isotypes of type I collagen were equally present in whole kidneys of heterozygous mice by immunohistochemistry and biochemical analysis, but the sclerotic glomerular collagen was at least 95-98% homotrimeric, suggesting homotrimeric type I collagen is the pathogenic isotype of type I collagen in glomerular disease. Although steady-state MMP and Col1a1 mRNA levels increased with the disease progression, we found these changes to be a secondary response to the deficient clearance of MMP-resistant homotrimers. Increased renal MMP expression was not sufficient to prevent homotrimeric type I collagen accumulation. |
