Extracellular matrix metalloproteinase inducer is expressed in the proximal tubular epithelial cells of the human kidney

Abstract

Matrix metalloproteinases (MMP) affect matrix remodelling, and extracellular matrix metalloproteinase inducer (EMMPRIN) has been reported to increase the levels of several MMP. However, the expression of EMMPRIN in the human kidney and its regulatory mechanisms are not well known. In this study, we examined EMMPRIN expression in the human kidney with the biopsied specimens, cultured proximal tubular epithelial cells (PTEC) and human mesangial cells (HMC). EMMPRIN expression was examined by immunofluorescent (IF) study, reverse transcription polymerase chain reaction, western blotting and enzyme-linked immunosorbent assay. We also examined soluble EMMPRIN in the conditioned medium of PTEC stimulated by various agents and its effect in the activities of MMP-2 and MMP-9. Also, IF study in the several kidney diseases was performed to elucidate its role in pathological condition. EMMPRIN expression was diffusely observed in the tubular epithelial cells of most patients and healthy adults, but was never observed in glomeruli. Cultured PTEC expressed EMMPRIN, while HMC did not. Soluble EMMPRIN was also detected by enzyme-linked immunosorbent assay in the conditioned medium of PTEC. Epidermal growth factor (50 ng/mL) and phorbol 12-myristate 13-acetate (10(-7) mol/L) stimulated the secretion of soluble EMMPRIN and increased the MMP-2 activity, although these agents did not increase the level of EMMPRIN mRNA. From the IF study, EMMPRIN expression was shown to decrease in tubulointerstitial nephritis. EMMPRIN is widely distributed in the tubular epithelial cells of the adult human kidney and may regulate MMP-2 activity via its secretion from PTEC.