Title

Deficient degradation of homotrimeric type I collagen, α1(I)3 glomerulopathy in oim mice

Document Type

Article

Publication Date

2011

Keywords

collagen, extracellular matrix, glomerular sclerosis, fibrosis, matrix metalloproteinase

Abstract

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.

Recommended Citation

Roberts-Pilgrim, Anna M., Elena Makareeva, Matthew H. Myles, Cynthia L. Besch-Williford, Amanda C. Brodeur, Andrew L. Walker, Sergey Leikin, Craig L. Franklin, and Charlotte L. Phillips. "Deficient degradation of homotrimeric type I collagen, α1 (I) 3 glomerulopathy in oim mice." Molecular genetics and metabolism 104, no. 3 (2011): 373-382.

DOI for the article

10.1016/j.ymgme.2011.07.025

Department

Biomedical Sciences

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