title: TGF-β1 induces human aortic vascular smooth muscle cell phenotype switch through PI3K/AKT/ID2 signaling.
abstract: The vascular smooth muscle cell (VSMC) phenotypic switch is considered to be the key pathophysiological change in various cardiovascular diseases, such as aortic dissection, atherosclerosis, and hypertension. The results in this study showed that TGF-β1 promotes the proliferation, migration and morphological changes of VSMC.TGF-β1 promoted the expressions of PI3K, P-PI3K, AKT, P-AKT, ID2, and OPN protein and suppressed the expressions of α-SMA and SM22α protein; the opposite results were observed for TGF-β1 inhibitor group, AKT inhibitor group and Combined inhibitors group. After the stimulation of TGF-β1 signaling, the mRNA levels of PI3K, AKT, ID2, and OPN were the highest, while the mRNA levels of α-SMA and SM22α were the lowest; the opposite results were found in the same groups above. These results suggested the PI3K/AKT/ID2 signaling pathway is involved in TGF-β1-mediated human aortic VSMC phenotypic switching, that is from a contractile to synthetic phenotype, and Combined inhibitors was more effective in inhibiting the phenotypic switch than a single inhibitor. The Combined inhibitors experiments may provide new avenues for the prevention and treatment of thoracic aortic dissection (TAD) that are based on the pathological effects of phenotypic switching.
authors.affiliation: Department of Thoracic Cardiovascular Surgery, Wuhan General Hospital of Guangzhou Command Wuhan, 430070, People's Republic of China.
authors.forename: Shui-Bo
authors.initials: SB
authors.lastname: Zhu
authors.affiliation: Department of Thoracic Cardiovascular Surgery, Wuhan General Hospital of Guangzhou Command Wuhan, 430070, People's Republic of China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Department of Thoracic Cardiovascular Surgery, Wuhan General Hospital of Guangzhou Command Wuhan, 430070, People's Republic of China.
authors.forename: Zi-Zi
authors.initials: ZZ
authors.lastname: Zhou
authors.affiliation: Department of Thoracic Cardiovascular Surgery, Wuhan General Hospital of Guangzhou Command Wuhan, 430070, People's Republic of China.
authors.forename: Er-Ping
authors.initials: EP
authors.lastname: Xi
authors.affiliation: Department of Thoracic Cardiovascular Surgery, Wuhan General Hospital of Guangzhou Command Wuhan, 430070, People's Republic of China.
authors.forename: Rong-Ping
authors.initials: RP
authors.lastname: Wang
authors.affiliation: Department of Thoracic Cardiovascular Surgery, Wuhan General Hospital of Guangzhou Command Wuhan, 430070, People's Republic of China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
keywords: ID2; PI3K/AKT; TGF-β1; Vascular smooth muscle cell; phenotype switch