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Mol Med Rep ; 15(5): 3225-3230, 2017 May.
Artículo en Inglés | MEDLINE | ID: mdl-28339082

RESUMEN

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.


Asunto(s)
Autofagia , Hipoxia de la Célula , Endocitosis , Metaloproteinasa 2 de la Matriz/metabolismo , Adenina/análogos & derivados , Adenina/farmacología , Autofagia/efectos de los fármacos , Línea Celular , Colágeno Tipo IV/análisis , Endocitosis/efectos de los fármacos , Ensayo de Inmunoadsorción Enzimática , Filipina/farmacología , Humanos , Túbulos Renales Proximales/citología , Túbulos Renales Proximales/efectos de los fármacos , Túbulos Renales Proximales/metabolismo , Metaloproteinasa 14 de la Matriz/genética , Metaloproteinasa 14 de la Matriz/metabolismo , Metaloproteinasa 2 de la Matriz/análisis , Metaloproteinasa 2 de la Matriz/genética , ARN Mensajero/metabolismo
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