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Your search keyword '"Xiaofei Lv"' showing total 3 results
Start Over Author "Xiaofei Lv" Journal acta pharmaceutica sinica b
3 results on '"Xiaofei Lv"'

2. TMEM16A inhibits angiotensin II-induced basilar artery smooth muscle cell migration in a WNK1-dependent manner

Author

Huaqing Zheng, Xiaolong Li, Xin Zeng, Chengcui Huang, Mingming Ma, Xiaofei Lv, Yajuan Zhang, Lu Sun, Guanlei Wang, Yanhua Du, and Yongyuan Guan

Subjects
TMEM16A, Integrin, RhoA/ROCK, VSMC migration, Vascular remodeling, WNK1, Therapeutics. Pharmacology, RM1-950
Abstract

Vascular smooth muscle cell (VSMC) migration plays a critical role in the pathogenesis of many cardiovascular diseases. We recently showed that TMEM16A is involved in hypertension-induced cerebrovascular remodeling. However, it is unclear whether this effect is related to the regulation of VSMC migration. Here, we investigated whether and how TMEM16A contributes to migration in basilar artery smooth muscle cells (BASMCs). We observed that AngII increased the migration of cultured BASMCs, which was markedly inhibited by overexpression of TMEM16A. TMEM16A overexpression inhibited AngII-induced RhoA/ROCK2 activation, and myosin light chain phosphatase (MLCP) and myosin light chain (MLC20) phosphorylation. But AngII-induced myosin light chain kinase (MLCK) activation was not affected by TMEM16A. Furthermore, a suppressed activation of integrinβ3/FAK pathway, determined by reduced integrinβ3 expression, FAK phosphorylation and F-actin rearrangement, was observed in TMEM16A-overexpressing BASMCs upon AngII stimulation. Contrary to the results of TMEM16A overexpression, silencing of TMEM16A showed the opposite effects. These in vitro results were further demonstrated in vivo in basilar arteries from VSMC-specific TMEM16A transgenic mice during AngII-induced hypertension. Moreover, we observed that the inhibitory effect of TMEM16A on BASMC migration was mediated by decreasing the activation of WNK1, a Cl−-sensitive serine/threonine kinase. In conclusion, this study demonstrated that TMEM16A suppressed AngII-induced BASMC migration, thus contributing to the protection against cerebrovascular remodeling during AngII-infused hypertension. TMEM16A may exert this effect by suppressing the RhoA/ROCK2/MLCP/MLC20 and integrinβ3/FAK signaling pathways via inhibiting WNK1. Our results suggest that TMEM16A may serve as a novel therapeutic target for VSMC migration-related diseases, such as vascular remodeling.

Published
2021
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3. TMEM16A inhibits angiotensin II-induced basilar artery smooth muscle cell migration in a WNK1-dependent manner

Author

Xin Zeng, Lu Sun, Yan-Hua Du, Cheng-cui Huang, Ming-Ming Ma, Hua-Qing Zheng, Yong-Yuan Guan, Ya-juan Zhang, Xiaofei Lv, Xiao-long Li, and Guan-Lei Wang

Subjects
MLCK, myosin light chain kinase, Myosin light-chain kinase, Vascular smooth muscle, RHOA, Smooth muscle cell migration, Integrin, RM1-950, MLC20, myosin light chain 20, 03 medical and health sciences, 0302 clinical medicine, MYPT1, myosin phosphatase target subunit 1, WNK1, with-no-lysine kinase 1, Vascular remodeling, ROCK2, General Pharmacology, Toxicology and Pharmaceutics, WNK1, BASMCs, basilar artery smooth muscle cells, 030304 developmental biology, TMEM16A, 0303 health sciences, biology, FAK, Chemistry, AngII, angiotensin II, Angiotensin II, Cell biology, F-actin, filamentous actin, SMTg, smooth muscle-specific TMEM16A transgenic mice, CaCC, Ca2+-activated chloride channel, FAK, focal adhesion kinase, MLCP, myosin light chain phosphates, 030220 oncology & carcinogenesis, Hypertension, VSMC migration, biology.protein, cardiovascular system, RhoA/ROCK, Original Article, Myosin-light-chain phosphatase, Therapeutics. Pharmacology, Signal transduction, VSMCs, vascular smooth muscle cells
Abstract

Vascular smooth muscle cell (VSMC) migration plays a critical role in the pathogenesis of many cardiovascular diseases. We recently showed that TMEM16A is involved in hypertension-induced cerebrovascular remodeling. However, it is unclear whether this effect is related to the regulation of VSMC migration. Here, we investigated whether and how TMEM16A contributes to migration in basilar artery smooth muscle cells (BASMCs). We observed that AngII increased the migration of cultured BASMCs, which was markedly inhibited by overexpression of TMEM16A. TMEM16A overexpression inhibited AngII-induced RhoA/ROCK2 activation, and myosin light chain phosphatase (MLCP) and myosin light chain (MLC20) phosphorylation. But AngII-induced myosin light chain kinase (MLCK) activation was not affected by TMEM16A. Furthermore, a suppressed activation of integrinβ3/FAK pathway, determined by reduced integrinβ3 expression, FAK phosphorylation and F-actin rearrangement, was observed in TMEM16A-overexpressing BASMCs upon AngII stimulation. Contrary to the results of TMEM16A overexpression, silencing of TMEM16A showed the opposite effects. These in vitro results were further demonstrated in vivo in basilar arteries from VSMC-specific TMEM16A transgenic mice during AngII-induced hypertension. Moreover, we observed that the inhibitory effect of TMEM16A on BASMC migration was mediated by decreasing the activation of WNK1, a Cl−-sensitive serine/threonine kinase. In conclusion, this study demonstrated that TMEM16A suppressed AngII-induced BASMC migration, thus contributing to the protection against cerebrovascular remodeling during AngII-infused hypertension. TMEM16A may exert this effect by suppressing the RhoA/ROCK2/MLCP/MLC20 and integrinβ3/FAK signaling pathways via inhibiting WNK1. Our results suggest that TMEM16A may serve as a novel therapeutic target for VSMC migration-related diseases, such as vascular remodeling., Graphical abstract This study suggests that modulation of TMEM16A expression and/or activity might be a novel strategy to prevent hypertension-induced vascular remodeling.Image 1

Published
2021

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