THROMBIN INCREASES CLUSTERIN MESSENGER-RNA IN GLOMERULAR EPITHELIAL AND MESANGIAL CELLS

Clusterin, a multifunctional protein with complement blocking activity , and fibrin, a product of thrombin's enzymatic activity, are present in the kidney during acute and chronic renal failure, The role of thro mbin in regulating clusterin mRNA in the kidney is not known. The effe ct of thrombin on clusterin mRNA expression was examined in rat glomer ular mesangial and glomerular epithelial cells, and cultured human ren al proximal tubular epithelial cells by northern blot. Thrombin (10(-8 ) M) increased clusterin mRNA levels two- to fourfold in glomerular me sangial, glomerular epithelial, and proximal tubule epithelial cells. This was a specific effect of thrombin receptor activation because pep tides corresponding to the tethered ligand of the thrombin receptor we re also able to increase clusterin mRNA levels. Epidermal growth facto r, insulin-like growth factor-1, and transforming growth factor-beta 1 had little or no effect on clusterin mRNA levels, The protein kinase C inhibitor RO-32-0432 (1 mu M) inhibited the thrombin-induced increas e in clusterin mRNA, suggesting that thrombin receptor activation may regulate renal clusterin mRNA levels through protein kinase C.