Effects of autophagy and endocytosis on the activity of matrix metalloproteinase‑2 in human renal proximal tubular cells under hypoxia

Yu,Wenmin; Wang,Zhi; Li,Yiping; Liu,Lei; Liu,Jing; Ding,Fenggan; Zhang,Xiaoyi; Cheng,Zhengyuan; Chen,Pingsheng

doi:10.3892/mmr.2017.6358

Effects of autophagy and endocytosis on the activity of matrix metalloproteinase‑2 in human renal proximal tubular cells under hypoxia

Authors:
- Wenmin Yu
- Zhi Wang
- Yiping Li
- Lei Liu
- Jing Liu
- Fenggan Ding
- Xiaoyi Zhang
- Zhengyuan Cheng
- Pingsheng Chen
View Affiliations

Affiliations: The School of Basic Medical Science, Jiujiang University/Jiujiang Key Laboratory of Translational Medicine, Jiujiang, Jiangxi 332000, P.R. China, Department of Pathology and Pathophysiology, Medical School of Southeast University, Nanjing, Jiangsu 210009, P.R. China
Published online on: March 22, 2017 https://doi.org/10.3892/mmr.2017.6358
Pages: 3225-3230

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

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.

View Figures

View References

1	Levey AS, Atkins R, Coresh J, Cohen EP, Collins AJ, Eckardt KU, Nahas ME, Jaber BL, Jadoul M, Levin A, et al: Chronic kidney disease as a global public health problem: Approaches and initiatives-a position statement from kidney disease improving global outcomes. Kidney Int. 72:247–259. 2007. View Article : Google Scholar : PubMed/NCBI
2	Schieppati A and Remuzzi G: Chronic renal diseases as a public health problem: Epidemiology, social and economic implications. Kidney Int Suppl. 98:S7–S10. 2005. View Article : Google Scholar
3	Jacobson HR: Chronic renal failure: Pathophysiology. Lancet. 338:419–423. 1991. View Article : Google Scholar : PubMed/NCBI
4	Luo X, Deng L, Lamsal LP, Xu W, Xiang C and Cheng L: AMP-activated protein kinase alleviates extracellular matrix accumulation in high glucose-induced renal fibroblasts through mTOR signaling pathway. Cell Physiol Biochem. 35:191–200. 2015. View Article : Google Scholar : PubMed/NCBI
5	Zhou X, Zhang J, Xu C and Wang W: Curcumin ameliorates renal fibrosis by inhibiting local fibroblast proliferation and extracellular matrix deposition. J Pharmacol Sci. 126:344–350. 2014. View Article : Google Scholar : PubMed/NCBI
6	Eddy AA: Molecular insights into renal interstitial fibrosis. J Am Soc Nephrol. 7:2495–2508. 1996.PubMed/NCBI
7	Ronco P and Chatziantoniou C: Matrix metalloproteinases and matrix receptors in progression and reversal of kidney disease: Therapeutic perspectives. Kidney Int. 74:873–878. 2008. View Article : Google Scholar : PubMed/NCBI
8	Basile DP, Fredrich K, Weihrauch D, Hattan N and Chilian WM: Angiostatin and matrix metalloprotease expression following ischemic acute renal failure. Am J Physiol Renal Physiol. 286:F893–F902. 2004. View Article : Google Scholar : PubMed/NCBI
9	Racca MA, Novoa PA, Rodríguez I, Della Vedova AB, Pellizas CG, Demarchi M and Donadio AC: Renal dysfunction and intragraft proMMP9 activity in renal transplant recipients with interstitial fibrosis and tubular atrophy. Transpl Int. 28:71–78. 2015. View Article : Google Scholar : PubMed/NCBI
10	Zhou TB, Qin YH, Lei FY, Huang WF and Drummen GP: Prohibitin attenuates oxidative stress and extracellular matrix accumulation in renal interstitial fibrosis disease. PLoS One. 8:e771872013. View Article : Google Scholar : PubMed/NCBI
11	DeCoux A, Lindsey ML, Villarreal F, Garcia RA and Schulz R: Myocardial matrix metalloproteinase-2: Inside out and upside down. J Mol Cell Cardiol. 77:64–72. 2014. View Article : Google Scholar : PubMed/NCBI
12	Fine LG and Norman JT: Chronic hypoxia as a mechanism of progression of chronic kidney diseases: From hypothesis to novel therapeutics. Kidney Int. 74:867–872. 2008. View Article : Google Scholar : PubMed/NCBI
13	Norman JT, Orphanides C, Garcia P and Fine LG: Hypoxia-induced changes in extracellular matrix metabolism in renal cells. Exp Nephrol. 7:463–469. 1999. View Article : Google Scholar : PubMed/NCBI
14	Orphanides C, Fine LG and Norman JT: Hypoxia stimulates proximal tubular cell matrix production via a TGF-beta1-independent mechanism. Kidney Int. 52:637–647. 1997. View Article : Google Scholar : PubMed/NCBI
15	Li J, Fan R, Zhao S, Liu L, Guo S, Wu N, Zhang W and Chen P: Reactive oxygen species released from hypoxic hepatocytes regulates MMP-2 expression in hepatic stellate cells. Int J Mol Sci. 12:2434–2447. 2011. View Article : Google Scholar : PubMed/NCBI
16	Bellot G, Garcia-Medina R, Gounon P, Chiche J, Roux D, Pouysségur J and Mazure NM: Hypoxia-induced autophagy is mediated through hypoxia-inducible factor induction of BNIP3 and BNIP3L via their BH3 domains. Mol Cell Biol. 29:2570–2581. 2009. View Article : Google Scholar : PubMed/NCBI
17	Mazure NM and Pouysségur J: Hypoxia-induced autophagy: Cell death or cell survival? Curr Opin Cell Biol. 22:177–180. 2010. View Article : Google Scholar : PubMed/NCBI
18	Michiels C: Physiological and pathological responses to hypoxia. Am J Pathol. 164:1875–1882. 2004. View Article : Google Scholar : PubMed/NCBI
19	Dada LA, Welch LC, Zhou G, Ben-Saadon R, Ciechanover A and Sznajder JI: Phosphorylation and ubiquitination are necessary for Na, K-ATPase endocytosis during hypoxia. Cell Signal. 19:1893–1898. 2007. View Article : Google Scholar : PubMed/NCBI
20	Kukulski W, Schorb M, Kaksonen M and Briggs JA: Plasma membrane reshaping during endocytosis is revealed by time-resolved electron tomography. Cell. 150:508–520. 2012. View Article : Google Scholar : PubMed/NCBI
21	Kim HN and Chung HS: Caveolin-1 inhibits membrane-type 1 matrix metalloproteinase activity. BMB Rep. 41:858–862. 2008. View Article : Google Scholar : PubMed/NCBI
22	Sato H, Takino T, Okada Y, Cao J, Shinagawa A, Yamamoto E and Seiki M: Matrix metalloproteinase expressed on the surface of invasive tumour cells. Nature. 370:61–65. 1994. View Article : Google Scholar : PubMed/NCBI
23	Butler GS, Butler MJ, Atkinson SJ, Will H, Tamura T, van Schade Westrum S, Crabbe T, Clements J, d'Ortho MP and Murphy G: The TIMP2 membrane type 1 metalloproteinase ‘receptor’ regulates the concentration and efficient activation of progelatinase A.A kinetic study. J Biol Chem. 273:871–880. 1998. View Article : Google Scholar : PubMed/NCBI
24	D'Amico G: Tubulo-interstitial damage in glomerular diseases: Its role in the progression of the renal damage. Nephrol Dial Transplant. 13:(Suppl 1). S80–S85. 1998. View Article : Google Scholar
25	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) Method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
26	Takahara T, Furui K, Funaki J, Nakayama Y, Itoh H, Miyabayashi C, Sato H, Seiki M, Ooshima A and Watanabe A: Increased expression of matrix metalloproteinase-II in experimental liver fibrosis in rats. Hepatology. 21:787–795. 1995. View Article : Google Scholar : PubMed/NCBI
27	Tanaka S, Tanaka T and Nangaku M: Hypoxia as a key player in the AKI-to-CKD transition. Am J Physiol Renal Physiol. 307:F1187–F1195. 2014. View Article : Google Scholar : PubMed/NCBI
28	Norman J and Orphanides C: Hypoxia alters extracellular matrix (ECM) synthesis and turnover in renal fibroblasts. J Am Soc Nephrol. 7:A25771996.
29	Chow AK, Cena J, El-Yazbi AF, Crawford BD, Holt A, Cho WJ, Daniel EE and Schulz R: Caveolin-1 inhibits matrix metalloproteinase-2 activity in the heart. J Mol Cell Cardiol. 42:896–901. 2007. View Article : Google Scholar : PubMed/NCBI
30	Schnitzer JE, Oh P, Pinney E and Allard J: Filipin-sensitive caveolae-mediated transport in endothelium: Reduced transcytosis, scavenger endocytosis, and capillary permeability of select macromolecules. J Cell Biol. 127:1217–1232. 1994. View Article : Google Scholar : PubMed/NCBI