Deficient degradation of homotrimeric type I collagen, α1(I)3 glomerulopathy in oim mice
| Autor: | Amanda C. Brodeur, Matthew H. Myles, Elena Makareeva, Sergey Leikin, Charlotte L. Phillips, Craig L. Franklin, Anna M. Roberts-Pilgrim, Andrew L. Walker, Cynthia Besch-Williford |
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| Rok vydání: | 2011 |
| Předmět: |
Endocrinology
Diabetes and Metabolism Kidney Glomerulus Biochemistry Article Collagen Type I Collagen receptor Extracellular matrix Mice Endocrinology Glomerulopathy Fibrosis Genetics medicine Animals Molecular Biology DNA Primers Reverse Transcriptase Polymerase Chain Reaction Chemistry Histological Techniques Glomerulosclerosis Osteogenesis Imperfecta medicine.disease Immunohistochemistry Molecular biology Mice Mutant Strains Collagen type I alpha 1 Mesangium Metalloproteases Azo Compounds Type I collagen |
| Zdroj: | Molecular Genetics and Metabolism. 104:373-382 |
| ISSN: | 1096-7192 |
| Popis: | Col1a2-deficient (oim) mice synthesize homotrimeric type I collagen due to nonfunctional proα2(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. |
| Databáze: | OpenAIRE |
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