RAS protein activator like 2 promotes the proliferation and migration of pulmonary artery smooth muscle cell through AKT/mammalian target of Rapamycin complex 1 pathway in pulmonary hypertension

References

• Kahraman BO, Savci S, Ozsoy I, et al. Effects of neuromuscular electrical stimulation in patients with pulmonary arterial hypertension: a randomized controlled pilot study. J Cardiol. 2020;75(6):702–708.
   PubMed Web of Science ®Google Scholar
• Schermuly RT, Ghofrani HA, Wilkins MR, et al. Mechanisms of disease: pulmonary arterial hypertension. Nat Rev Cardiol. 2011;8(8):443–455.
   PubMed Web of Science ®Google Scholar
• Simonneau G, Montani D, Celermajer DS, et al. Haemodynamic definitions and updated clinical classification of pulmonary hypertension. Eur Respir J. 2019;53(1):1801913.
   PubMed Web of Science ®Google Scholar
• Zhang L, Wang Y, Wu G, et al. Blockade of JAK2 protects mice against hypoxia-induced pulmonary arterial hypertension by repressing pulmonary arterial smooth muscle cell proliferation. Cell Prolif. 2020;53(2):e12742.
   PubMed Web of Science ®Google Scholar
• Lajoie AC, Lauziere G, Lega JC, et al. Combination therapy versus monotherapy for pulmonary arterial hypertension: a meta-analysis. Lancet Respir Med. 2016;4(4):291–305.
   PubMed Web of Science ®Google Scholar
• Humbert M, Sitbon O, Chaouat A, et al. Survival in patients with idiopathic, familial, and anorexigen-associated pulmonary arterial hypertension in the modern management era. Circulation. 2010;122(2):156–163.
   PubMed Web of Science ®Google Scholar
• Zhang Q, Li W, Zhu Y, et al. Activation of AMPK inhibits Galectin-3-induced pulmonary artery smooth muscle cells proliferation by upregulating hippo signaling effector YAP. Mol Cell Biochem. 2021;476(8):3037–3049.
   PubMed Web of Science ®Google Scholar
• Nasim MT, Ogo T, Chowdhury HM, et al. BMPR-II deficiency elicits pro-proliferative and anti-apoptotic responses through the activation of TGFbeta-TAK1-MAPK pathways in PAH. Hum Mol Genet. 2012;21(11):2548–2558.
   PubMed Web of Science ®Google Scholar
• Zhang W, Shu C, Li Q, et al. Adiponectin affects vascular smooth muscle cell proliferation and apoptosis through modulation of the mitofusin-2-mediated Ras-Raf-Erk1/2 signaling pathway. Mol Med Rep. 2015;12(3):4703–4707.
   PubMed Web of Science ®Google Scholar
• Lawrence MC, Jivan A, Shao C, et al. The roles of MAPKs in disease. Cell Res. 2008;18(4):436–442.
   PubMed Web of Science ®Google Scholar
• Pan Y, Tong JHM, Lung RWM, et al. RASAL2 promotes tumor progression through LATS2/YAP1 axis of hippo signaling pathway in colorectal cancer. Mol Cancer. 2018;17(1):102.
   PubMedGoogle Scholar
• Zhou B, Zhu W, Jiang X, et al. RASAL2 plays inconsistent roles in different cancers. Front Oncol. 2019;9:1235.
   PubMed Web of Science ®Google Scholar
• Feng M, Bao Y, Li Z, et al. RASAL2 activates RAC1 to promote triple-negative breast cancer progression. J Clin Invest. 2014;124(12):5291–5304.
   PubMed Web of Science ®Google Scholar
• Zhu X, Xie S, Xu T, et al. Rasal2 deficiency reduces adipogenesis and occurrence of obesity-related disorders. Mol Metab. 2017;6(6):494–502.
   PubMed Web of Science ®Google Scholar
• Hui K, Yue Y, Wu S, et al. The expression and function of RASAL2 in renal cell carcinoma angiogenesis. Cell Death Dis. 2018;9(9):881.
   PubMedGoogle Scholar
• Ciuclan L, Bonneau O, Hussey M, et al. A novel murine model of severe pulmonary arterial hypertension. Am J Respir Crit Care Med. 2011;184(10):1171–1182.
   PubMed Web of Science ®Google Scholar
• Wan N, Rong W, Zhu W, et al. Tregs-derived interleukin 35 attenuates endothelial proliferation through STAT1 in pulmonary hypertension. Ann Transl Med. 2021;9(11):926.
   PubMed Web of Science ®Google Scholar
• Wang J, Feng W, Li F, et al. SphK1/S1P mediates TGF-beta1-induced proliferation of pulmonary artery smooth muscle cells and its potential mechanisms. Pulm Circ. 2019;9(1):2045894018816977.
   Web of Science ®Google Scholar
• Sun X, Li S, Gan X, et al. Wild-type p53-induced phosphatase 1 promotes vascular smooth muscle cell proliferation and neointima hyperplasia after vascular injury via p-adenosine 5ʹ-monophosphate-activated protein kinase/mammalian target of rapamycin complex 1 pathway. J Hypertens. 2019;37(11):2256–2268.
   PubMed Web of Science ®Google Scholar
• Babicheva A, Makino A, Yuan JX. mTOR signaling in pulmonary vascular disease: pathogenic role and therapeutic target. Int J Mol Sci. 2021;22(4):2144.
   PubMed Web of Science ®Google Scholar
• Li Y, Yang L, Dong L, et al. Crosstalk between the Akt/mTORC1 and NF-kappaB signaling pathways promotes hypoxia-induced pulmonary hypertension by increasing DPP4 expression in PASMCs. Acta Pharmacol Sin. 2019;40(10):1322–1333.
   PubMed Web of Science ®Google Scholar
• Kim JH, Kim N. Signaling pathways in osteoclast differentiation. Chonnam Med J. 2016;52(1):12–17.
   PubMedGoogle Scholar
• Wang Y, Bai Y, Qin L, et al. Interferon-gamma induces human vascular smooth muscle cell proliferation and intimal expansion by phosphatidylinositol 3-kinase dependent mammalian target of rapamycin raptor complex 1 activation. Circ Res. 2007;101(6):560–569.
   PubMed Web of Science ®Google Scholar
• Fang JF, Zhao HP, Wang ZF, et al. Upregulation of RASAL2 promotes proliferation and metastasis, and is targeted by miR-203 in hepatocellular carcinoma. Mol Med Rep. 2017;15(5):2720–2726.
   PubMed Web of Science ®Google Scholar
• Liu J, Duan Z, Guo W, et al. Targeting the BRD4/FOXO3a/CDK6 axis sensitizes AKT inhibition in luminal breast cancer. Nat Commun. 2018;9(1):5200.
   PubMedGoogle Scholar
• Zuo W, Liu N, Zeng Y, et al. Luteolin ameliorates experimental pulmonary arterial hypertension via suppressing Hippo-YAP/PI3K/AKT signaling pathway. Front Pharmacol. 2021;12:663551.
   PubMed Web of Science ®Google Scholar
• Yang H, Lu Y, Zhu Y, et al. Integrated weighted gene co-expression network analysis uncovers STAT1(signal transducer and activator of transcription 1) and IFI44L (interferon-induced protein 44-like) as key genes in pulmonary arterial hypertension. Bioengineered. 2021;12(1):6021–6034.
   PubMed Web of Science ®Google Scholar
• Jellusova J. The role of metabolic checkpoint regulators in B cell survival and transformation. Immunol Rev. 2020;295(1):39–53.
   PubMed Web of Science ®Google Scholar
• Fernandes H, Moura J, Carvalho E. mTOR signaling as a regulator of hematopoietic stem cell fate. Stem Cell Rev Rep. 2021;17(4):1312–1322.
   PubMed Web of Science ®Google Scholar
• Aghamohammadzadeh R, Zhang YY, Stephens TE, et al. Up-regulation of the mammalian target of rapamycin complex 1 subunit Raptor by aldosterone induces abnormal pulmonary artery smooth muscle cell survival patterns to promote pulmonary arterial hypertension. FASEB J. 2016;30(7):2511–2527.
   PubMed Web of Science ®Google Scholar
• Krymskaya VP, Snow J, Cesarone G, et al. mTOR is required for pulmonary arterial vascular smooth muscle cell proliferation under chronic hypoxia. FASEB J. 2011;25(6):1922–1933.
   PubMed Web of Science ®Google Scholar
• Jain M, Dhanesha N, Doddapattar P, et al. Smooth muscle cell-specific fibronectin-EDA mediates phenotypic switching and neointimal hyperplasia. J Clin Invest. 2020;130(1):295–314.
   PubMed Web of Science ®Google Scholar
• Betz C, Hall MN. Where is mTOR and what is it doing there? J Cell Biol. 2013;203(4):563–574.
   PubMed Web of Science ®Google Scholar
• Tang H, Wu K, Wang J, et al. Pathogenic role of mTORC1 and mTORC2 in pulmonary hypertension. JACC Basic Transl Sci. 2018;3(6):744–762.
   PubMedGoogle Scholar
• Tang H, Chen J, Fraidenburg DR, et al. Deficiency of Akt1, but not Akt2, attenuates the development of pulmonary hypertension. Am J Physiol Lung Cell Mol Physiol. 2015;308(2):L208–220.
   PubMed Web of Science ®Google Scholar
• Laplante M, Sabatini DM. mTOR signaling in growth control and disease. Cell. 2012;149(2):274–293.
   PubMed Web of Science ®Google Scholar