Type I collagen glomerulopathy: postnatal collagen deposition follows glomerular maturation.
In chronic renal disease, the progressive accumulation of collagen and other extracellular matrix proteins in the mesangium results in fibrosis, glomerulosclerosis, and eventual renal failure. Mice deficient in proalpha2(I) collagen are not only a model of osteogenesis imperfecta but also accumulate fibrillar homotrimeric type I collagen in the mesangium. This accumulation spreads to the subendothelial space in the peripheral capillary loops. Picosirius red staining of kidney sections demonstrates that in comparison to wild-type mice, Col1a2-deficient homozygous and heterozygous mice exhibit abnormal glomerular collagen deposition in a gene dosage-dependent manner. The glomerulopathy initiates during the first postnatal week, appears progressive following the pattern of glomerular maturation and results in albuminuria in severely affected animals. In situ hybridization revealed no gross differences in steady-state proalpha1(I) and proalpha2(I) collagen mRNA levels among the three genotypes. Quantitative reverse transcriptase-polymerase chain reaction, however, using whole kidney sections showed a twofold increase in steady-state proalpha1(I) collagen mRNA in 1-month homozygous Col1a2-deficient animals compared with wild-type and heterozygous animals. We suggest that glomerular collagen deposition seen in the osteogenesis imperfecta model mice is, in part, owing to pretranslational mechanisms and may represent an over compensation of wound healing.
Brodeur
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AC
[1] 1Department of Biochemistry, University of Missouri, Columbia, Missouri 65212, USA.
Wirth
D A
DA
Franklin
C L
CL
Reneker
L W
LW
Miner
J H
JH
Phillips
C L
CL
D000419:Albuminuria / Q000209:etiology; D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development / Q000378:metabolism*; D003094:Collagen / Q000172:deficiency* / Q000235:genetics; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism*; D000090602:Collagen Type I, alpha 1 Chain; D006579:Heterozygote; D006706:Homeostasis; D007674:Kidney Diseases / Q000209:etiology* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D007678:Kidney Glomerulus / Q000254:growth & development* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D008854:Microscopy, Electron; D012333:RNA, Messenger / Q000378:metabolism
D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D012333:RNA, Messenger; D003094:Collagen