Effects of autophagy and endocytosis on the activity of matrix metalloproteinase­2 in human renal proximal tubular cells under hypoxia.

Tubulointerstitial fibrosis is characterized by tubular atrophy with basement membrane thickening and accumulation of interstitial extracellular matrix (ECM). A decrease in the activity of matrix metalloproteinase­2 (MMP­2) may promote this process. Although proximal tubular cells are sensitive to oxygen deprivation, whether cellular autophagy or endocytosis induced by hypoxia can alter the activity of MMP­2 remains to be elucidated. The aim of the present study was to investigate whether autophagy and endocytosis induced by hypoxia can have an effect on the activity of MMP­2 in HK­2 cells. The investigations involved exposing the HK­2 cell line to an autophagy inhibitor, 3­MA, or an endocytotic inhibitor, filipin. The mRNA expression of MMP­2 was elevated in the hypoxic milieu. Furthermore, it was found that filipin increased the activity of MMP­2 under hypoxia. These results suggested that autophagy and endocytosis were potential mediators for the altered expression of MMP­2, and endocytosis was a potential target for regulating the activity of MMP­2. These data suggested that hypoxia may be an important pro­fibrogenic stimulus, which acts in part via endocytosis.