Objective:To investigate the effects of ripasudil on proliferation and migration of human pulmonary arterial smooth cells(HPASMCs)induced by platelet-derived growth factor(PDGF)-BB and the mechanisms underlying. Methods:Cultured HPASMCs were divided into four groups:the control group,the PDGF-BB-treated group,the PDGF-BB and ripasudil-treated group and the ripasudil-treated group. CCK-8 was applied to investigate cell viability and EdU assay was used to evaluate the proliferation of HPASMCs. Transwell assay was employed to examine cell migration. The expression of matrix metalloproteinase-2(MMP-2)was determined by real-time PCR and Western blot. The levels of phosphorylated myosin phosphatase target subunit 1(MYPT1),extracellar regulated protein kinases 1/2(ERK1/2),p38,and protein kinase B(PKB/Akt)were detected by Western blot. Results:Compared with the control group,ripasudil blocked the proliferation and migration of HPASMCs challenged by PDGF-BB(P<0.01). Ripasudil suppressed PDGF-BB-induced upregulation of MMP-2(P<0.05). Moreover,ripasudil inhibited PDGF-BB-induced phosphorylation of MYPT1,ERK1/2,p38,and Akt(P<0.05). Conclusion:Ripasudil significantly inhibited PDGF-BB-induced proliferation and migration of HPASMCs,which might be attributed to the inhibition of MYPT1,ERK1/2,p38 and Akt. Ripasudil,a Rho kinase inhibitor,might be a potential therapeutic option in PAH.
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Sun Defang, Kong Hui, Xie Weiping, Wang Hong. Effects of ripasudil on proliferation and migration of human pulmonary arterial smooth cells induced by platelet⁃derived growth factor⁃BB[J].,2018,(7):878-884.