caa a22 4500 606233903 CHVBK 20210128101234.0 cr unu---uuuuu 210128e20150401xx s 000 0 eng 10.1007/s11010-014-2298-6 doi (NATIONALLICENCE)springer-10.1007/s11010-014-2298-6 Transient receptor potential vanilloid 4 inhibits rat HSC-T6 apoptosis through induction of autophagy [Elektronische Daten] [Lei Zhan, Yang Yang, Tao-Tao Ma, Cheng Huang, Xiao-Ming Meng, Lei Zhang, Jun Li] Hepatic stellate cell (HSC) activation is a significant event in the development of liver fibrosis. Promoting the activated HSCs apoptosis contributes to the reversal of liver fibrosis. Autophagy is considered to be critical for many cellular and pathological processes including liver fibrosis. Transient receptor potential vanilloid 4 (TRPV4), another member of the transient receptor potential (TRP) channel, is proved to be a vital modulator in regulating HSC proliferation during liver fibrosis. However, the precise mechanism of TRPV4 on HSC apoptosis is still unclear. Here, we explored the role of TRPV4 in regulating HSC-T6 cell apoptosis. Our study detected that the expressions of TRPV4 mRNA and protein were dramatically increased in HSC-T6 in response to TGF-β1 stimulation by qRT-PCR and Western blot. Moreover, the HSC-T6 transfected with si-TRPV4 increased apoptosis and inhibited autophagy. In addition, the HSC-T6 treated with 4α-phorbol 12,13-didecanoate results in suppression of apoptosis and increase of autophagy. Furthermore, we indicated that TRPV4 induces autophagy by regulating AKT signaling pathway. In addition, we found that blockade of autophagy by chemical antagonists chloroquine (CQ) leads to increased apoptosis. Furthermore, blocking autophagy by CQ did not lead to a distinct change with or without TRPV4 over-expression. These results indicated that TRPV4 could inhibit HSCs apoptosis partially by regulating autophagy-dependent AKT signaling pathway activation. Springer Science+Business Media New York, 2015 Hepatic stellate cells nationallicence Transient receptor potential vanilloid 4 nationallicence Apoptosis nationallicence Autophagy nationallicence AKT signaling pathway nationallicence 4α-PDD : 4α-Phorbol 12,13-didecanoate nationallicence AO : Acridine orange nationallicence CQ : Chloroquine nationallicence DMEM : Dulbecco's modified Eagle's medium nationallicence DMSO : Dimethyl sulfoxide nationallicence ECM : Extracellular matrix nationallicence FBS : Fetal bovine serum nationallicence HSCs : Hepatic stellate cells nationallicence MFBLC : Myofibroblast-like cells nationallicence MTT : 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide nationallicence PBS : Phosphate-buffered saline nationallicence PVDF : Polyvinylidene fluoride film nationallicence qRT-PCR : Quantitative real-time PCR nationallicence SDS-PAGE : Sodium dodecyl sulfate polyacrylamide gel electrophoresis nationallicence siRNA : Small interfering RNA nationallicence TGF-β1 : Transforming growth factor-beta 1 nationallicence TRP : Transient receptor potential nationallicence TRPM7 : Transient receptor potential melastatin 7 nationallicence TPRV4 : Transient receptor potential vanilloid receptor 4 nationallicence Zhan Lei The Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Anhui Medical University, Hefei, China aut Yang Yang The Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Anhui Medical University, Hefei, China aut Ma Tao-Tao The Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Anhui Medical University, Hefei, China aut Huang Cheng The Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Anhui Medical University, Hefei, China aut Meng Xiao-Ming The Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Anhui Medical University, Hefei, China aut Zhang Lei The Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Anhui Medical University, Hefei, China aut Li Jun The Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Anhui Medical University, Hefei, China aut Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 402/1-2(2015-04-01), 9-22 0300-8177 402:1-2<9 2015 402 11010 https://doi.org/10.1007/s11010-014-2298-6 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s11010-014-2298-6 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Zhan Lei The Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Anhui Medical University, Hefei, China aut NATIONALLICENCE 700 1- Yang Yang The Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Anhui Medical University, Hefei, China aut NATIONALLICENCE 700 1- Ma Tao-Tao The Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Anhui Medical University, Hefei, China aut NATIONALLICENCE 700 1- Huang Cheng The Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Anhui Medical University, Hefei, China aut NATIONALLICENCE 700 1- Meng Xiao-Ming The Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Anhui Medical University, Hefei, China aut NATIONALLICENCE 700 1- Zhang Lei The Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Anhui Medical University, Hefei, China aut NATIONALLICENCE 700 1- Li Jun The Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Anhui Medical University, Hefei, China aut NATIONALLICENCE 773 0- Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 402/1-2(2015-04-01), 9-22 0300-8177 402:1-2<9 2015 402 11010