1. Academic Validation
  2. Verapamil inhibits ureteral scar formation by regulating CaMK II-mediated Smad pathway

Verapamil inhibits ureteral scar formation by regulating CaMK II-mediated Smad pathway

  • Chem Biol Interact. 2021 Sep 1;346:109570. doi: 10.1016/j.cbi.2021.109570.
Ming-Qiang Zeng 1 Wei Xiao 1 Ke Yang 1 Zhi-Yong Gao 1 Jian-Song Wang 1 Qiang Lu 1 Xi Guo 1 Yuan-Wei Li 2 Wu-Xiong Yuan 3
Affiliations

Affiliations

  • 1 Department of Urology, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, 410005, Hunan Province, PR China.
  • 2 Department of Urology, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, 410005, Hunan Province, PR China. Electronic address: xxuccheew123@163.com.
  • 3 Department of Urology, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, 410005, Hunan Province, PR China. Electronic address: wwuxxyuu789@163.com.
Abstract

Verapamil is reported to prevent scar formation. However, whether verapamil is involved in the ureteral stricture scar and the underlying mechanism need further investigation. Fibroblasts were isolated from ureteral scar tissues. TGF-β1 stimulation was used to induce fibrosis of fibroblasts. Inhibition of CaMK II was achieved by shRNA transfection. CCK-8 was performed to evaluate cell viability. qRT-PCR was applied to determine the level of mRNA while western blotting was used to determine the level of proteins. Immunofluorescence was used to detect the level of vimentin, collagen I and collagen III. Primary fibroblasts was successfully isolated from ureteral scar tissues. TGF-β1 stimulation was capable to induce collagen production and fibrosis in primary fibroblasts while inhibition of CaMK II attenuate collagen production. Overexpression of wild type CaMK II lead to further increase of collagen production upon TGF-β1 stimulation while the mutated CaMK II did not exert this promotion. Treatment of verapamil inhibits TGF-β1 induced collagen production via inhibiting CaMK II. In present study, we revealed a vital role of Verapamil and CaMK II in the formation of ureteral scar. Verapamil inhibited TGF-β1 induced collagen fiber formation by regulating CaMK II. Our finding might provide new insight into mechanism of prevention and treatment of ureteral scar.

Keywords

CaMK II; TGF-β1/Smads; Ureteral scar; Verapamil.

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