A factor from damaged rat kidney stimulates collagen biosynthesis by mesangial cells.
Rats were administered CCl4, a well-defined nephrotoxin, for 20 weeks to produce glomerular sclerosis. Tubular degeneration and necrosis with interstitial fibrosis was clearly evident by histological examination. Kidneys were homogenized in phosphate-buffered saline and a collagen synthesis-stimulating factor was isolated by Sephadex G-50 gel filtration. The 5 kDa component stimulated both type I and type IV procollagen synthesis by mesangial cells and type I procollagen synthesis by rat skin fibroblasts. In each cell type, 2-6-fold increases in procollagen protein production or cell proliferation was noted. The steady-state levels of mRNA encoding for procollagen alpha 1(I) and procollagen alpha 1(IV) chains in mesangial cells were determined by by hybridization to their corresponding cDNA clones. The type I procollagen mRNA was elevated 1.4-fold compared to a 1.6-fold increase in mRNA encoding for type IV procollagen. The similar properties and chemical characteristics of this fibrogenic factor with a factor from fibrotic liver suggests they are the same and that a common endogenous collagen synthesis stimulator may be present in fibrosing organs, thus providing a driving force for collagen over-production.
Ohyama
K
K
Department of Medicine, University of Tennessee, Memphis.
Seyer
J M
JM
Raghow
R
R
Kang
A H
AH
D000818:Animals; D002252:Carbon Tetrachloride Poisoning / Q000378:metabolism*; D002478:Cells, Cultured; D005260:Female; D005355:Fibrosis / Q000378:metabolism; D005920:Glomerular Mesangium / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D009336:Necrosis / Q000378:metabolism; D011347:Procollagen / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012598:Sclerosis / Q000378:metabolism
D011347:Procollagen; D012333:RNA, Messenger