Abstract
Tubulointerstitial fibrosis leads to tubular basement membrane thickening and accumulation of interstitial extracellular matrix (ECM). Matrix metallopeptidase-2 (MMP-2) is involved in the breakdown of ECM. Chronic hypoxia often occurs in the kidney tissues of patients with chronic kidney disease. Our previous study reported the effect of autophagy and endocytosis on MMP-2 activity in hypoxia-treated HK-2 cells. In this study, the relationship between the Ras-related protein Rab-7a (RAB7) and MMP-2 activity was further investigated. RAB7 overexpression decreased MMP-2 activity. In contrast, the results for RAB7 knockdown displayed the opposite pattern. Short hairpin RNA technology was used to knockdown Caveolin-1 (Cav-1) or Beclin-1 (Bec-1) in HK-2 cells. The two genes displayed differential effects on MMP-2 activity. Cav-1 and RAB7 interference increased MMP-2 activity. This study suggested that autophagy and endocytosis, RAB7, Cav-1, and Bec-1 may serve as potential mediators for altered MMP-2 activity.
Highlights
Renal tubulointerstitial fibrosis is the pathological feature of almost all chronic kidney diseases (CKDs) [1]
The green fluorescent protein (GFP)-RAB7 lentiviral vector was infected into HK-2 cells under a fluorescence microscope
Previous studies have demonstrated that hypoxia may affect the cellular components of renal tubules, which maintain normal metabolism and function properly, renal proximal tubule cells are the primary target of hypoxic damage [27]
Summary
Renal tubulointerstitial fibrosis is the pathological feature of almost all chronic kidney diseases (CKDs) [1]. Tubulointerstitial fibrosis leads to the thickening of the basement membrane of tubules and interstitial extracellular matrix (ECM) accumulation [2,3]. In patients with CKD, MMP-2 activity in renal tissues decreases, leading to progressive renal insufficiency and organ failure [7]. Numerous studies have reported that the activity of MMP-2 in proximal tubule cells decreases during hypoxia, but the underlying mechanism remains unclear [10]. We had reported earlier that hypoxia decreases MMP-2 activity [11,12]. Recent studies have demonstrated that autophagy has a close and complex relationship with hypoxia, but the underlying mechanism was not reported earlier [13]. Researchers have reported that autophagy serves a dual role in hypoxia-induced cell damage [14].
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