Transient Receptor Potential Channel Canonical Type 3 Deficiency Antagonizes Myofibroblast Transdifferentiation In Vivo

Weijie Xia; Qianran Wang; Yuangang Lu; Yingru Hu; Xingcun Zhang; Junbo Zhang; Dongfang Liu; Jinlin Song; Zhiming Zhu; Daoyan Liu; Hengshu Zhang

doi:10.1155/2020/1202189

Transient Receptor Potential Channel Canonical Type 3 Deficiency Antagonizes Myofibroblast Transdifferentiation In Vivo

Biomed Res Int. 2020 Mar 5:2020:1202189. doi: 10.1155/2020/1202189. eCollection 2020.

Authors

Weijie Xia¹, Qianran Wang², Yuangang Lu³, Yingru Hu⁴, Xingcun Zhang³, Junbo Zhang³, Dongfang Liu², Jinlin Song⁵, Zhiming Zhu⁴, Daoyan Liu⁴, Hengshu Zhang¹

Affiliations

¹ Department of Burn & Plastic Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
² Department of Endocrinology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing 400010, China.
³ Department of Plastic & Cosmetic Surgery, Research Institute of Surgery, Daping Hospital, Third Military Medical University, Chongqing 400042, China.
⁴ Department of Hypertension and Endocrinology, Center for Hypertension and Metabolic Diseases, Daping Hospital, Third Military Medical University, Chongqing Institute of Hypertension, Chongqing 400042, China.
⁵ School of Dental Medicine, Chongqing Medical University, Chongqing 400016, China.

Abstract

Objective: Myofibroblast transformation has been shown to be associated with the reactive oxygen species- (ROS-) producing enzyme NADPH oxidase (Nox4). Inhibition of transient receptor potential channel canonical type 3 (TRPC3) attenuates mitochondrial calcium handling and ROS production in the vasculature of hypertensive rats. However, it remains elusive whether TRPC3 regulates mitochondrial calcium and ROS production and participates in myofibroblast transdifferentiation during wound healing.

Methods and results: In this study, we demonstrated that activation of TRPC3 by transforming growth factor β (TGFβ (TGFαSMA). Inhibition of TRPC3 with its specific inhibitor, Pyr3, significantly decreased TGFβ (TGFαSMA). Inhibition of TRPC3 with its specific inhibitor, Pyr3, significantly decreased TGFβ (TGFβ (TGFTrpc3^-/- mice exhibited significantly attenuated myofibroblast transdifferentiation, as demonstrated by decreased αSMA). Inhibition of TRPC3 with its specific inhibitor, Pyr3, significantly decreased TGFβ (TGFβ (TGFTrpc3^-/- mice exhibited significantly attenuated myofibroblast transdifferentiation, as demonstrated by decreased Trpc3^+/+ mice. In addition, Trpc3^-/- mice exhibited significantly attenuated myofibroblast transdifferentiation, as demonstrated by decreased.

Conclusions: Our data indicate that TGFβ1-mediated activation of TRPC3 enhances mitochondrial calcium and ROS production, which promotes myofibroblast transdifferentiation and HTS formation. Inhibition of the TRPC3-mediated Nox4/pSmad2/3 pathway may be a useful strategy to limit HTS formation after injury.β (TGF.

MeSH terms

Actins / metabolism
Adult
Animals
Calcium / metabolism
Cell Transdifferentiation / physiology*
Female
Humans
Male
Mice
Mice, Knockout
Middle Aged
Mitochondria / metabolism
Myofibroblasts / metabolism*
Myofibroblasts / pathology
Pyrazoles / pharmacology
Reactive Oxygen Species / metabolism
TRPC Cation Channels / antagonists & inhibitors*
TRPC Cation Channels / genetics*
TRPC Cation Channels / metabolism*
Transforming Growth Factor beta / metabolism
Young Adult

Substances

Actins
Pyrazoles
Reactive Oxygen Species
TRPC Cation Channels
TRPC3 cation channel
Transforming Growth Factor beta
alpha-smooth muscle actin, mouse
ethyl-1-(4-(2*3*3-trichloroacrylamide)phenyl)-5-(trifluoromethyl)-1H-pyrazole-4-carboxylate
Calcium