Vascular smooth muscle cell(VSMC) migration plays a critical role in the pathogenesis of many cardiovascular diseases.We recently showed that TMEM16 A is involved in hypertensioninduced cerebrovascular remodeling.Howe...Vascular smooth muscle cell(VSMC) migration plays a critical role in the pathogenesis of many cardiovascular diseases.We recently showed that TMEM16 A is involved in hypertensioninduced cerebrovascular remodeling.However,it is unclear whether this effect is related to the regulation of VSMC migration.Here,we investigated whether and how TMEM16 A 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 TMEM16 A.TMEM16 A overexpression inhibited AngⅡ-induced RhoA/ROCK2 activation,and myosin light chain phosphatase(MLCP)and myosin light chain(MLC20) phosphorylation.But AnsⅡ-induced myosin light chain kinase(MLCK)activation was not affected by TMEM16 A.Furthermore,a suppressed activation of integrinβ3/FAK pathway,determined by reduced integrinβ3 expression,FAK phosphorylation and F-actin rearrangement,was observed in TMEM16 A-overexpressing BASMCs upon AngⅡ stimulation.Contrary to the results of TMEM16 A overexpression,silencing of TMEM16 A showed the opposite effects.These in vitro results were further demonstrated in vivo in basilar arteries from VSMC-specific TMEM10 A transgenic mice during AngⅡ-induced hypertension.Moreover,we observed that the inhibitory effect of TMEM16 A on BASMC migration was mediated by decreasing the activation of WNK1,a Cl^(-)-sensitive serine/threonine kinase.In conclusion,this study demonstrated that TMEM16 A suppressed AnsⅡ-induced BASMC migration,thus contributing to the protection against cerebrovascular remodeling during AngⅡ-infused hypertension.TMEM16 A may exert this effect by suppressing the RhoA/ROCK2/MLCP/MLC20 and integrinβ3/FAK signaling pathways via inhibiting WNK1.Our results suggest that TMEM16 A may serve as a novel therapeutic target for VSMC migration-related diseases,such as vascular remodeling.展开更多
The authors regret that there were some picture errors in the Fig.1D,G,I,Fig.4L,Fig.6C,H and Supporting Information Fig.S1A owing to copy and paste mistakes when preparing the representative images.The revisions do no...The authors regret that there were some picture errors in the Fig.1D,G,I,Fig.4L,Fig.6C,H and Supporting Information Fig.S1A owing to copy and paste mistakes when preparing the representative images.The revisions do not affect the data value,significant difference,and conclusions of the current work and the description of the whole article.The original data of this figure have been provided to the Editorial Office,and the Editorial Office or the corresponding authors can be contacted for original data access.展开更多
The authors regret that picture errors were found in the Fig.II,Fig.4L and Fig.6C owing to copy and paste mistakes during the process of using AI tools to check published images.Due to the large number of original ima...The authors regret that picture errors were found in the Fig.II,Fig.4L and Fig.6C owing to copy and paste mistakes during the process of using AI tools to check published images.Due to the large number of original images,these errors were not detected by manual inspection when preparing the corrected representative images previously.展开更多
基金supported by the National Natural Science Foundation of China (grant Nos. 81872858, 81773721, 81573422, and 81903598)。
文摘Vascular smooth muscle cell(VSMC) migration plays a critical role in the pathogenesis of many cardiovascular diseases.We recently showed that TMEM16 A is involved in hypertensioninduced cerebrovascular remodeling.However,it is unclear whether this effect is related to the regulation of VSMC migration.Here,we investigated whether and how TMEM16 A 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 TMEM16 A.TMEM16 A overexpression inhibited AngⅡ-induced RhoA/ROCK2 activation,and myosin light chain phosphatase(MLCP)and myosin light chain(MLC20) phosphorylation.But AnsⅡ-induced myosin light chain kinase(MLCK)activation was not affected by TMEM16 A.Furthermore,a suppressed activation of integrinβ3/FAK pathway,determined by reduced integrinβ3 expression,FAK phosphorylation and F-actin rearrangement,was observed in TMEM16 A-overexpressing BASMCs upon AngⅡ stimulation.Contrary to the results of TMEM16 A overexpression,silencing of TMEM16 A showed the opposite effects.These in vitro results were further demonstrated in vivo in basilar arteries from VSMC-specific TMEM10 A transgenic mice during AngⅡ-induced hypertension.Moreover,we observed that the inhibitory effect of TMEM16 A on BASMC migration was mediated by decreasing the activation of WNK1,a Cl^(-)-sensitive serine/threonine kinase.In conclusion,this study demonstrated that TMEM16 A suppressed AnsⅡ-induced BASMC migration,thus contributing to the protection against cerebrovascular remodeling during AngⅡ-infused hypertension.TMEM16 A may exert this effect by suppressing the RhoA/ROCK2/MLCP/MLC20 and integrinβ3/FAK signaling pathways via inhibiting WNK1.Our results suggest that TMEM16 A may serve as a novel therapeutic target for VSMC migration-related diseases,such as vascular remodeling.
文摘The authors regret that there were some picture errors in the Fig.1D,G,I,Fig.4L,Fig.6C,H and Supporting Information Fig.S1A owing to copy and paste mistakes when preparing the representative images.The revisions do not affect the data value,significant difference,and conclusions of the current work and the description of the whole article.The original data of this figure have been provided to the Editorial Office,and the Editorial Office or the corresponding authors can be contacted for original data access.
文摘The authors regret that picture errors were found in the Fig.II,Fig.4L and Fig.6C owing to copy and paste mistakes during the process of using AI tools to check published images.Due to the large number of original images,these errors were not detected by manual inspection when preparing the corrected representative images previously.
