title: Transient receptor potential vanilloid 4 inhibits rat HSC-T6 apoptosis through induction of autophagy.
abstract: 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.
authors.affiliation: The Key Laboratory of Anti-inflammatory and Immune Medicine, Ministry of Education, Anhui Medical University, Hefei, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhan
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.forename: Tao-Tao
authors.initials: TT
authors.lastname: Ma
authors.forename: Cheng
authors.initials: C
authors.lastname: Huang
authors.forename: Xiao-Ming
authors.initials: XM
authors.lastname: Meng
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.forename: Jun
authors.initials: J
authors.lastname: Li
mesh_terms: D000818:Animals; D017209:Apoptosis; D001343:Autophagy; D002460:Cell Line; D015870:Gene Expression; D055166:Hepatic Stellate Cells / Q000502:physiology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction; D050916:TRPV Cation Channels / Q000502:physiology*; D053773:Transforming Growth Factor beta1 / Q000502:physiology
chemical_list: D050916:TRPV Cation Channels; D053773:Transforming Growth Factor beta1; C486577:Trpv4 protein, rat; D051057:Proto-Oncogene Proteins c-akt