Septin4 Prevents PDGF-BB-induced HAVSMC Phenotypic Transformation, Proliferation and Migration by Promoting SIRT1-STAT3 Deacetylation and Dephosphorylation

Zhang, Naijin; Zhang, Ying; You, Shilong; Tian, Yichen; Lu, Saien; Cao, Liu; Sun, Yingxian

doi:10.7150/ijbs.39843

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Int J Biol Sci 2020; 16(4):708-718. doi:10.7150/ijbs.39843 This issue Cite

Research Paper

Septin4 Prevents PDGF-BB-induced HAVSMC Phenotypic Transformation, Proliferation and Migration by Promoting SIRT1-STAT3 Deacetylation and Dephosphorylation

Naijin Zhang¹, Ying Zhang^1,2, Shilong You¹, Yichen Tian¹, Saien Lu¹, Liu Cao^2✉, Yingxian Sun^1✉

1. Department of Cardiology, the First Hospital of China Medical University, Shenyang, Liaoning, China.
2. Key Laboratory of Medical Cell Biology, Ministry of Education; Institute of Translational Medicine, China Medical University; Liaoning Province Collaborative Innovation Center of Aging Related Disease Diagnosis and Treatment and Prevention, Shenyang, Liaoning, China.

Citation:

Zhang N, Zhang Y, You S, Tian Y, Lu S, Cao L, Sun Y. Septin4 Prevents PDGF-BB-induced HAVSMC Phenotypic Transformation, Proliferation and Migration by Promoting SIRT1-STAT3 Deacetylation and Dephosphorylation. Int J Biol Sci 2020; 16(4):708-718. doi:10.7150/ijbs.39843. https://www.ijbs.com/v16p0708.htm

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Abstract

SIRT1 and STAT3 are key to human aortic vascular smooth muscle cells (HAVSMCs) proliferation, migration and phenotypic transformation, but the regulatory mechanism of SIRT1-STAT3 in this process is still unclear. Septin4 is a cytoskeleton-related protein that regulates oxidative stress-vascular endothelial injury. However, the role and underlying mechanism of Septin4 in atherosclerosis remains unknown. Here, we revealed the role and mechanism of Septin4 in regulating SIRT1-STAT3 in atherosclerosis. We determined that the expression of Septin4 were markedly increased in Apoe^-/- atherosclerosis mice and PDGF-BB-induced HAVSMCs. Knockdown of Septin4 significantly increased PDGF-BB-induced HAVSMCs proliferation, migration and phenotypic transformation, while overexpression of Septin4 had the opposite effects. Mechanically, co-immunoprecipitation results demonstrated that Septin4 was a novel interacting protein of STAT3 and SIRT1. Septin4 formed a complex with SIRT1-STAT3, enhancing the interaction between SIRT1 and STAT3, ensuing promoting SIRT1-regulated STAT3-K685 deacetylation and STAT3-Y705 dephosphorylation, which inhibited PDGF-BB-induced HAVSMCs proliferation, migration and phenotype transformation. Therefore, our findings provide novel insights into the prevention and treatment of atherosclerosis.

Keywords: Septin4, STAT3, SIRT1, Atherosclerosis.

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APA

Zhang, N., Zhang, Y., You, S., Tian, Y., Lu, S., Cao, L., Sun, Y. (2020). Septin4 Prevents PDGF-BB-induced HAVSMC Phenotypic Transformation, Proliferation and Migration by Promoting SIRT1-STAT3 Deacetylation and Dephosphorylation. International Journal of Biological Sciences, 16(4), 708-718. https://doi.org/10.7150/ijbs.39843.

ACS

Zhang, N.; Zhang, Y.; You, S.; Tian, Y.; Lu, S.; Cao, L.; Sun, Y. Septin4 Prevents PDGF-BB-induced HAVSMC Phenotypic Transformation, Proliferation and Migration by Promoting SIRT1-STAT3 Deacetylation and Dephosphorylation. Int. J. Biol. Sci. 2020, 16 (4), 708-718. DOI: 10.7150/ijbs.39843.

NLM

CSE

Zhang N, Zhang Y, You S, Tian Y, Lu S, Cao L, Sun Y. 2020. Septin4 Prevents PDGF-BB-induced HAVSMC Phenotypic Transformation, Proliferation and Migration by Promoting SIRT1-STAT3 Deacetylation and Dephosphorylation. Int J Biol Sci. 16(4):708-718.

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