Identification of cellular origin of type I collagen in glomeruli of rats with crescentic glomerulonephritis induced by anti-glomerular basement membrane antibody

Background. Type I collagen is an interstitial collagen, which is not prese nt in normal glomeruli. As type I collagen was observed in advanced glomeru lar lesions, it appears to be associated with deterioration of renal functi on. However, the origins of cells expressing type I collagen mRNA in glomer uli of diseased kidneys remains controversial. Methods. We examined the expression of type I collagen in glomeruli at prot ein and mRNA levels in rat crescentic glomerulonephritis induced by anti-gl omerular basement membrane (GBM) antibody. In addition, in situ hybridizati on and immunohistochemical staining of serial sections were performed to id entify the cellular origin of type I collagen in glomeruli. Results. Semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) in isolated glomeruli showed that mRNA expression of type I collag en was remarkably increased on days 7, 14, and 28 after anti-GBM antibody i njection (12.2+/-1.4, 20.2+/-2.1 and 14.6+/-1.0-fold over day 0, respective ly). Immunofluorescence for type I collagen demonstrated marked staining in the fibrocellular and fibrous crescents, and weak staining within glomerul ar mesangial areas. In close association with mRNA levels analysed by RT-PC R, in situ hybridization revealed predominant presence of alpha1(I) collage n mRNA in cells within crescentic areas and Bowman's capsules. Serial secti on analysis for immunostaining and in situ hybridization showed that some a lpha1(I) collagen mRNA-positive cells were also positive for cytokeratin. I n contrast, no alpha1(I) collagen mRNA-positive cells were stained by ED-1 and podocalyxin. Conclusions. It appears that increased expression of type I collagen at the protein and mRNA levels in glomeruli is involved in the progression of glo merulonephritis. At least in this crescentic model, parietal epithelial cel ls (PECs) may partially contribute to the dysregulated production of type I collagen, which leads to glomerulosclerosis.