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TRIM32 inhibits the proliferation and migration of pulmonary artery smooth muscle cells through the inactivation of PI3K/Akt pathway in pulmonary arterial hypertension

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Abstract

Pulmonary arterial hypertension (PAH) is a progressive and fetal cardiovascular disease. Tripartite motif 32 (TRIM32) is a member of TRIM family that has been found to be involved in cardiovascular disease. However, the role of TRIM32 in PAH remains unclear. Here we investigated the effects of TRIM32 on hypoxia-induced pulmonary artery smooth muscle cells (PASMCs) in vitro. Our results showed that TRIM32 protein level in the plasma samples from PAH patients was decreased as compared with healthy volunteers. Exposure to hypoxia condition caused a significant decrease in TRIM32 expression in PASMCs. Overexpression of TRIM32 inhibited hypoxia-induced proliferation and migration of PASMCs. TRIM32 overexpression elevated the increased apoptotic rate and caspase-3 activity in hypoxia-induced PASMCs. Moreover, overexpression of TRIM32 reversed hypoxia-induced down-regulation of myocardin, SM 22 and calponin, as well as up-regulation of osteopontin (OPN). Whereas, TRIM32 knockdown shwed the opposite effect. Furthermore, overexpression of TRIM32 inhibited hypoxia-induced activation of PI3K/Akt with decreased phosphorylated level of PI3K and Akt. Additionally, activation of PI3K/Akt by IGF-1 treatment reversed the effects of TRIM32 on hypoxia-induced PASMCs. In conclusion, these findings indicated that TRIM32 was involved in the development of PAH through regulating the proliferation, migration, apoptosis and dedifferentiation of PASMCs, which might be mediated by the PI3K/Akt signaling pathway. Thus, TRIM32 might be a potential target for PAH treatment.

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Acknowledgements

This study was supported by the Basic research plan of Natural Science in Shaanxi Province (2020JM-378) in China.

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Authors and Affiliations

  1. Department of Cardiovascular Medicine, The First Affiliated Hospital of Xi’an Jiaotong University, No. 277 West Yanta Road, Xi’an, Shaanxi, 710061, China

    Zhi Hu, Qiang Song, Hui Ma, Yaozhang Guo, Tingting Zhang, Hang Xie & Xiaohui Luo

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  1. Zhi Hu
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  2. Qiang Song
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  3. Hui Ma
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  4. Yaozhang Guo
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  5. Tingting Zhang
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  6. Hang Xie
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  7. Xiaohui Luo
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Contributions

Zhi Hu designed and wrote this manuscript. Qiang Song, Hui Ma and Yaozhang Guo performed experiments. Tingting Zhang analyzed the data. Hang Xie and Xiaohui Luo revised the language of the manuscript; all the authors approved the manuscript for submission.

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Correspondence to Zhi Hu.

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Hu, Z., Song, Q., Ma, H. et al. TRIM32 inhibits the proliferation and migration of pulmonary artery smooth muscle cells through the inactivation of PI3K/Akt pathway in pulmonary arterial hypertension. J Bioenerg Biomembr 53, 309–320 (2021). https://doi.org/10.1007/s10863-021-09880-w

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