Class II phosphatidylinositol 3-kinase α and β isoforms are required for vascular smooth muscle Rho activation, contraction and blood pressure regulation in mice

The journal of physiological sciences

article

Shahidul Islam¹  Kazuaki Yoshioka¹  Sho Aki¹  Kazuhiro Ishimaru¹  Hiroki Yamada¹  Noriko Takuwa¹  Yoh Takuwa¹ 

[1] Department of Physiology, Kanazawa University Graduate School of Medical Sciences;Department of Health Science, Ishikawa Prefectural University

关键词: Class II phosphatidylinositol 3-kinase;    Vascular smooth muscle;    Contraction;    Rho;    Blood pressure;   

DOI  :  10.1186/s12576-020-00745-2

来源: Springer

【 摘 要 】

Class II phosphatidylinositol 3-kinases (PI3K), PI3K-C2α and PI3K-C2β, are involved in cellular processes including endocytosis, cilia formation and autophagy. However, the role of PI3K-C2α and PI3K-C2β at the organismal level is not well understood. We found that double knockout (KO) mice with both smooth muscle-specific KO of PI3K-C2α and global PI3K-C2β KO, but not single KO mice of either PI3K-C2α or PI3K-C2β, exhibited reductions in arterial blood pressure and substantial attenuation of contractile responses of isolated aortic rings. In wild-type vascular smooth muscle cells, double knockdown of PI3K-C2α and PI3K-C2β but not single knockdown of either PI3K markedly inhibited contraction with reduced phosphorylation of 20-kDa myosin light chain and MYPT1 and Rho activation, but without inhibition of the intracellular Ca2+ mobilization. These data indicate that PI3K-C2α and PI3K-C2β play the redundant but essential role for vascular smooth muscle contraction and blood pressure regulation mainly through their involvement in Rho activation.

【 授权许可】

Unknown