TMEM16A regulates portal vein smooth muscle cell proliferation in portal hypertension

  • Authors:
    • Xi Zeng
    • Ping Huang
    • Mingkai Chen
    • Shiqian Liu
    • Nannan Wu
    • Fang Wang
    • Jing Zhang
  • View Affiliations

  • Published online on: November 8, 2017     https://doi.org/10.3892/etm.2017.5466
  • Pages:1062-1068
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Abstract

The aim of the present study was to elucidate the effect of transmembrane protein 16A (TMEM16A) on portal vein smooth muscle cell (PVSMC) proliferation associated with portal vein remodeling in portal hypertension (PHT). Sprague‑Dawley rats were subjected to bile duct ligation to establish a rat model of liver cirrhosis and PHT. Sham‑operated animals served as controls. At 8 weeks after bile duct ligation, the extent of liver fibrosis and the portal vein wall thickness were assessed using hematoxylin‑eosin staining. The protein expression levels of TMEM16A, extracellular signal‑regulated kinase 1 and 2 (ERK1/2) and phosphorylated ERK1/2 (p‑ERK1/2) in the portal vein were detected by immunohistochemistry and western blotting. In vitro, the lentivirus vectors were constructed and transfected into PVSMCs to upregulate the expression of TMEM16A. Isolated rat primary PVSMCs were treated with a small molecule inhibitor of TMEM16A, T16A‑inhA01. Cell cycle was detected by flow cytometry. The activity of TMEM16A in the portal vein isolated from bile duct ligated rats was decreased, while the expression level of p‑ERK1/2 was increased. However, in vitro, upregulation of TMEM16A promoted the proliferation PVSMCs, while inhibition of TMEM16A channels inhibited the proliferation of PVSMCs. The results indicated that TMEM16A contributes to PVSMCs proliferation in vitro, but in vivo, it may be a negative regulator of cell proliferation influenced by numerous factors.

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January 2018
Volume 15 Issue 1

Print ISSN: 1792-0981
Online ISSN:1792-1015

2016 Impact Factor: 1.261
Ranked #50/128 Medicine Research and Experimental
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APA
Zeng, X., Huang, P., Chen, M., Liu, S., Wu, N., Wang, F., & Zhang, J. (2018). TMEM16A regulates portal vein smooth muscle cell proliferation in portal hypertension. Experimental and Therapeutic Medicine, 15, 1062-1068. https://doi.org/10.3892/etm.2017.5466
MLA
Zeng, X., Huang, P., Chen, M., Liu, S., Wu, N., Wang, F., Zhang, J."TMEM16A regulates portal vein smooth muscle cell proliferation in portal hypertension". Experimental and Therapeutic Medicine 15.1 (2018): 1062-1068.
Chicago
Zeng, X., Huang, P., Chen, M., Liu, S., Wu, N., Wang, F., Zhang, J."TMEM16A regulates portal vein smooth muscle cell proliferation in portal hypertension". Experimental and Therapeutic Medicine 15, no. 1 (2018): 1062-1068. https://doi.org/10.3892/etm.2017.5466