TMEM16A regulates portal vein smooth muscle cell proliferation in portal hypertension

Abstract

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.

TMEM16B determines cholecystokinin sensitivity of intestinal vagal afferents of nodose neurons

“…Primary antibodies. Goat polyclonal anti-Ano1 (catalog sc-69343, lot E2714), which recognizes epitope amino acids 825-875 of human Ano1, is validated by Sun et al (73) in pulmonary artery protein lysates and several labs in other tissues (74)(75)(76)(77)(78)(79). It shows a band of approximately 114 kDa in Western blot.…”

Expression of transmembrane protein 41A is associated with metastasis via the modulation of E‑cadherin in radically resected gastric cancer

“…The TMEM protein superfamily comprises >310 different members, including membrane proteins, which are extensively expressed on cell and lysosomal membranes, and the endoplasmic reticulum, are strongly associated with membrane integrity, transport and signaling pathways (20). An increasing number of studies have investigated the TMEM superfamily and tumor-associated genes, particularly the oncogenes, TMEM16a (7,8), TMEM17a and TMEM17b (9) and the tumor suppressor gene TMEM100 (21,22). Certain TMEM genes have been reported to be involved in the development and metastasis of GC, such as TMEM16a (20).…”

“…An increasing number of studies have investigated the TMEM superfamily and tumor-associated genes, particularly the oncogenes, TMEM16a (7,8), TMEM17a and TMEM17b (9) and the tumor suppressor gene TMEM100 (21,22). Certain TMEM genes have been reported to be involved in the development and metastasis of GC, such as TMEM16a (20).…”

“…The transmembrane (TMEM) protein superfamily is a group of transmembrane proteins that participate in particular signaling pathways and tumor development associated with established oncogenes, particularly TMEM16a (7,8), TMEM17a and TMEM17b (9). The associated proteins serve roles in colorectal, ovarian and bladder cancer.…”

Recent advances in TMEM16A: Structure, function, and disease

“…These data indicated that activation of TMEM16A can limit the proliferation of pulmonary endothelial cells. Interestingly, X. Zeng et al () found that upregulation of TMEM16A contributes to portal vein smooth muscle cells proliferation in vitro. However, in vivo, the protein expression level of TMEM16A was significantly decreased in portal hypertension rat models (X. Zeng et al, ).…”