Synthesis of type VI collagen by cultured glomerular cells and comparison of its regulation by glucose and other factors with that of type IV collagen.
Homogeneous cultures of calf glomerular mesangial and endothelial cells were found to be active in the synthesis of type VI as well as type IV collagen in contrast to the epithelial cells that were devoted primarily to the production of the latter collagen. Studies with rat mesangial cells indicated that they responded to high glucose (20 mM) in the medium by a significant (P < 0.001) increase in type VI collagen synthesis as measured by the production of the protein and its mRNA level, both of which were closely correlated to each other and to glucose consumption. Similar observations were made with type IV collagen, but the enhanced formation of this protein was not as rapidly apparent as that of type VI and, moreover, could not be as readily reversed on restoration of the glucose to a physiological level (5 mM). Evaluation of a number of other agents indicated that although mannitol had no effect, L-glucose and NaCl significantly stimulated synthesis of both type VI and IV collagens and glucose consumption. Insulin-like growth factor I and aldosterone, on the other hand, also increased glucose consumption but brought about an enhancement of only type IV collagen production, suggesting that the two collagens are independently regulated. This possibility was supported by our observation that pyruvate, which was actively taken up by the cells, selectively stimulated type IV collagen production.(ABSTRACT TRUNCATED AT 250 WORDS)
Wakisaka
M
M
Department of Biological Chemistry, Harvard Medical School, Boston, Massachusetts.
Spiro
M J
MJ
Spiro
R G
RG
D000450:Aldosterone / Q000494:pharmacology; D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis* / Q000302:isolation & purification; D004591:Electrophoresis, Polyacrylamide Gel; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D005920:Glomerular Mesangium / Q000187:drug effects / Q000378:metabolism; D005947:Glucose / Q000378:metabolism* / Q000494:pharmacology*; D006019:Glycolysis / Q000187:drug effects; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D007678:Kidney Glomerulus / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D008353:Mannitol / Q000494:pharmacology; D008970:Molecular Weight; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013045:Species Specificity; D013997:Time Factors
D012333:RNA, Messenger; D008353:Mannitol; D000450:Aldosterone; D007334:Insulin-Like Growth Factor I; D003094:Collagen; D005947:Glucose