Effects of autophagy and endocytosis on the activity of matrix metalloproteinase‑2 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 metalloproteinase‑2 (MMP‑2) 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 MMP‑2 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 MMP‑2 in HK‑2 cells. The investigations involved exposing the HK‑2 cell line to an autophagy inhibitor, 3‑MA, or an endocytotic inhibitor, filipin. The mRNA expression of MMP‑2 was elevated in the hypoxic milieu. Furthermore, it was found that filipin increased the activity of MMP‑2 under hypoxia. These results suggested that autophagy and endocytosis were potential mediators for the altered expression of MMP‑2, and endocytosis was a potential target for regulating the activity of MMP‑2. These data suggested that hypoxia may be an important pro‑fibrogenic stimulus, which acts in part via endocytosis.
The School of Basic Medical Science, Jiujiang University/Jiujiang Key Laboratory of Translational Medicine, Jiujiang, Jiangxi 332000, P.R. China.
Wenmin
W
Yu
Department of Pathology and Pathophysiology, Medical School of Southeast University, Nanjing, Jiangsu 210009, P.R. China.
Zhi
Z
Wang
Department of Pathology and Pathophysiology, Medical School of Southeast University, Nanjing, Jiangsu 210009, P.R. China.
Yiping
Y
Li
Department of Pathology and Pathophysiology, Medical School of Southeast University, Nanjing, Jiangsu 210009, P.R. China.
Lei
L
Liu
Department of Pathology and Pathophysiology, Medical School of Southeast University, Nanjing, Jiangsu 210009, P.R. China.
Jing
J
Liu
Department of Pathology and Pathophysiology, Medical School of Southeast University, Nanjing, Jiangsu 210009, P.R. China.
Fenggan
F
Ding
Department of Pathology and Pathophysiology, Medical School of Southeast University, Nanjing, Jiangsu 210009, P.R. China.
Xiaoyi
X
Zhang
Department of Pathology and Pathophysiology, Medical School of Southeast University, Nanjing, Jiangsu 210009, P.R. China.
Zhengyuan
Z
Cheng
Department of Pathology and Pathophysiology, Medical School of Southeast University, Nanjing, Jiangsu 210009, P.R. China.
Pingsheng
P
Chen
D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D001343:Autophagy / Q000187:drug effects; D015687:Cell Hypoxia; D002460:Cell Line; D024141:Collagen Type IV / Q000032:analysis; D004705:Endocytosis / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D005372:Filipin / Q000494:pharmacology; D006801:Humans; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D053511:Matrix Metalloproteinase 14 / Q000235:genetics / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism
D024141:Collagen Type IV; D012333:RNA, Messenger; C025946:3-methyladenine; D005372:Filipin; D020778:Matrix Metalloproteinase 2; C507086:MMP14 protein, human; D053511:Matrix Metalloproteinase 14; D000225:Adenine