Next Article in Journal
Lung Macrophage Phenotypes and Functional Responses: Role in the Pathogenesis of COPD
Previous Article in Journal
Glycosylation as a Main Regulator of Growth and Death Factor Receptors Signaling
Article

Hypoxia Activates Src and Promotes Endocytosis Which Decreases MMP-2 Activity and Aggravates Renal Interstitial Fibrosis

Department of Pathology and Pathophysiology, Medical School, Southeast University, Dingjiaqiao 87, Gulou District, Nanjing 210009, China
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2018, 19(2), 581; https://doi.org/10.3390/ijms19020581
Received: 21 December 2017 / Revised: 22 January 2018 / Accepted: 12 February 2018 / Published: 15 February 2018
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
The aggravation of renal interstitial fibrosis in the advanced-stage of chronic kidney disease is related to decreased matrix metalloproteinase-2 (MMP-2) activity, which is induced by hypoxia in the kidney; however, the specific mechanism remains unclear. We previously demonstrated that inhibition of Caveolin-1, a key gene involved in endocytosis, increased MMP-2 activity in hypoxic HK-2 cells. It has been reported that activated Src (phospho-Src Tyr416) is a key molecule in multiple fibrotic pathways. However, whether Src functions on the regulation of Caveolin-1 and MMP-2 activity in hypoxic HK-2 cells remains poorly understood. To explore the underlying mechanism, a rat model of renal interstitial fibrosis was established, then we observed obvious hypoxia in fibrotic kidney tissue and the protein levels of phospho-Src and Caveolin-1 increased, while MMP-2 activity decreased. Next, we treated HK-2 cells with the phospho-Src inhibitor PP1. Compared with normal cells grown in hypoxia, in cells treated with PP1, the protein levels of phospho-Src and Caveolin-1 decreased, as did the protein levels of the MMP-2-activity-regulated molecules RECK (reversion-inducing-cysteine-rich protein with kazal motifs) and TIMP-2 (tissue inhibitor of metalloproteinase-2), while the protein level of MT1-MMP (membrane type 1-matrix metalloproteinase) increased and MMP-2 activity was enhanced. Therefore, hypoxia promotes the phosphorylation of Src and phospho-Src can enhance the endocytosis of HK-2 cells, which leads to decreased MMP-2 activity and aggravates renal interstitial fibrosis. View Full-Text
Keywords: renal interstitial fibrosis; hypoxia; endocytosis; MMP-2 activity renal interstitial fibrosis; hypoxia; endocytosis; MMP-2 activity
Show Figures

Graphical abstract

MDPI and ACS Style

Cheng, Z.; Liu, L.; Wang, Z.; Cai, Y.; Xu, Q.; Chen, P. Hypoxia Activates Src and Promotes Endocytosis Which Decreases MMP-2 Activity and Aggravates Renal Interstitial Fibrosis. Int. J. Mol. Sci. 2018, 19, 581. https://doi.org/10.3390/ijms19020581

AMA Style

Cheng Z, Liu L, Wang Z, Cai Y, Xu Q, Chen P. Hypoxia Activates Src and Promotes Endocytosis Which Decreases MMP-2 Activity and Aggravates Renal Interstitial Fibrosis. International Journal of Molecular Sciences. 2018; 19(2):581. https://doi.org/10.3390/ijms19020581

Chicago/Turabian Style

Cheng, Zhengyuan; Liu, Lei; Wang, Zhi; Cai, Yingying; Xu, Qing; Chen, Pingsheng. 2018. "Hypoxia Activates Src and Promotes Endocytosis Which Decreases MMP-2 Activity and Aggravates Renal Interstitial Fibrosis" Int. J. Mol. Sci. 19, no. 2: 581. https://doi.org/10.3390/ijms19020581

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Search more from Scilit
 
Search
Back to TopTop