TENASCIN IS SYNTHESIZED AND SECRETED BY RAT MESANGIAL CELLS IN CULTURE AND IS PRESENT IN EXTRACELLULAR-MATRIX IN HUMAN GLOMERULAR-DISEASES

Tenascin (TN) is a large oligomeric protein recently described as a co mponent of the extracellular matrix. The distribution of TN in adult k idney tissue has not been adequately evaluated, but preliminary data h ave suggested that TN is variably seen in rare mesangial areas and in stroma surrounding some tubules. The enlargement of the mesangial matr ix (mesangial sclerosis) is a common feature of many renal diseases an d is thought to be partially related to oversynthesis of the normal co mponents of the mesangial matrix (collagen type IV, laminin, fibronect in, and heparan sulfate proteoglycans) by mesangial cells. However, th e possibility that mesangial cells are also the source of other extrac ellular matrix proteins that participate in the process of mesangial s clerosis has not been explored. In this study, the synthesis of TN by cultured rat mesangial cells was documented by the following observati ons: (1) Northern hybridization of total RNA extracted from mesangial cells showed two distinct species of TN mRNA; (2) immunoblotting of th e protein extracted from the conditioned medium demonstrated four TN p rotein bands; (3) immunoblotting of the protein extracted from the mes angial cell lysate demonstrated at least four TN protein bands; and (4 ) immunohistochemical techniques identified TN within the cytoplasm of mesangial cells and in the surrounding extracellular matrix. It was a lso found that normal rat and human glomeruli showed global, diffuse m esangial staining for TN by immunohistochemical techniques and that, i n glomerular diseases characterized by the expansion of the mesangial matrix such as diabetic glomerulosclerosis, the expanded mesangial mat rix was stained positive for TN. These findings suggest that mesangial cells in culture synthesize TN and that TN is a component of the mesa ngial matrix; moreover, increased synthesis of TN may play a significa nt role in the pathogenesis of mesangial sclerosis and glomerulosclero sis.