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 cell s were found to be active in the synthesis of type VI as well as type IV collagen in contrast to the epithelial eels that were devoted prima rily to the production of the tatter collagen. Studies with rat mesang ial cells indicated that they responded to high glucose (20 mM) in the medium by a significant (P < 00.001) increase in type VI collagen syn thesis as measured by the production of the protein and its mRNA level , both of which were closely correlated to each other and to glucose c onsumption. 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 res toration of the glucose to a physiological level (5 mM). Evaluation of a number of other agents indicated that although mannitol had no effe ct, L-glucose and NaCl significantly stimulated synthesis of both type VI and IV collagens and glucose consumption. Insulin-like growth fact or I and aldosterone, on the other hand, also increased glucose consum ption but brought about an enhancement of only type IV collagen produc tion, suggesting that the two collagens are independently regulated. T his possibility was supported by our observation that pyruvate, which was actively taken up by the cells, selectively stimulated type IV col lagen production. Although the details of the regulation of these two major glomerular extracellular matrix components have not yet been def ined, it is apparent that mesangial cells in culture reflect the enhan ced formation of type VI and type IV collagen, which is evident in the diabetic glomerular lesions.