Tenascin is synthesized and secreted by rat mesangial cells in culture and is present in extracellular matrix in human glomerular diseases

Abstract

Tenascin (TN) is a large oligomeric protein recently described as a component of the extracellular matrix. The distribution of TN in adult kidney tissue has not been adequately evaluated, but preliminary data have suggested that TN is variably seen in rare mesangial areas and in stroma surrounding some tubules. The enlargement of the mesangial matrix (mesangial sclerosis) is a common feature of many renal diseases and is thought to be partially related to oversynthesis of the normal components of the mesangial matrix (collagen type IV, laminin, fibronectin, and heparan sulfate proteoglycans) by mesangial cells. However, the possibility that mesangial cells are also the source of other extracellular matrix proteins that participate in the process of mesangial sclerosis has not been explored. In this study, the synthesis of TN by cultured rat mesangial cells was documented by the following observations: (1) Northern hybridization of total RNA extracted from mesangial cells showed two distinct species of TN mRNA; (2) immunoblotting of the protein extracted from the conditioned medium demonstrated four TN protein bands; (3) immunoblotting of the protein extracted from the mesangial 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 also found that normal rat and human glomeruli showed global, diffuse mesangial staining for TN by immunohistochemical techniques and that, in glomerular diseases characterized by the expansion of the mesangial matrix such as diabetic glomerulosclerosis, the expanded mesangial matrix was stained positive for TN. These findings suggest that mesangial cells in culture synthesize TN and that TN is a component of the mesangial matrix; moreover, increased synthesis of TN may play a significant role in the pathogenesis of mesangial sclerosis and glomerulosclerosis.