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

• Published in: The journal of physiological sciences Vol. 70; no. 1; p. 18
• Main Authors: Islam, Shahidul, Yoshioka, Kazuaki, Aki, Sho, Ishimaru, Kazuhiro, Yamada, Hiroki, Takuwa, Noriko, Takuwa, Yoh
• Format: Journal Article
• Language: English
• Published: Japan BioMed Central 19-03-2020
• Subjects: 1-Phosphatidylinositol 3-kinase; Animals; Aorta; Autophagy; Blood pressure; Blood Pressure - physiology; Calcium (intracellular); Calcium - metabolism; Calcium mobilization; Cell adhesion & migration; Cell growth; Cells, Cultured; Cilia; Class II Phosphatidylinositol 3-Kinases - genetics; Class II Phosphatidylinositol 3-Kinases - metabolism; Coronary vessels; Disease Models, Animal; Endocytosis; Isoenzymes; Isoforms; Kinases; Mice; Mice, Knockout; Muscle contraction; Muscle Contraction - physiology; Muscle, Smooth, Vascular - cytology; Muscle, Smooth, Vascular - enzymology; Muscle, Smooth, Vascular - metabolism; Muscle, Smooth, Vascular - physiology; Myosin; Original Paper; Phagocytosis; Phosphorylation; Proteins; rho GTP-Binding Proteins - genetics; rho GTP-Binding Proteins - metabolism; Smooth muscle; United States > US; Japan; Rho; Blood pressure; Class II phosphatidylinositol 3-kinase; Vascular smooth muscle; Contraction
• ISSN: 1880-6546; 1880-6562
• DOI: 10.1186/s12576-020-00745-2

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 Ca
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.