Irisin/peroxisome proliferator-activated receptor alpha signaling pathway mediates vascular smooth muscle cell proliferation in mice

doi:10.12307/2023.493

Abstract

Abstract: BACKGROUND: Irisin is released from fibronectin type III domain containing 5 (FNDC5) after hydrolysis and modification. In addition to regulating the main physiological functions of glucolipid metabolism, irisin also has the ability to regulate the proliferation and apoptosis of a variety of cells.
OBJECTIVE: To investigate the role and mechanism of irisin/peroxisome proliferator-activated receptor alpha (PPARα) signaling pathway mediated heme oxygenase-1 in regulating the balance between proliferation and apoptosis of vascular smooth muscle cells.
METHODS: FNDC5 overexpression and silencing lentivirus vector were used to transfect vascular smooth muscle cells to increase or inhibit irisin production, and an in vitro cell model was constructed. There were seven groups: blank control group, overexpressed empty vector group, FNDC5 overexpression group, overexpressed empty vector+PPARα inhibitor (GW6471) group, FNDC5 overexpression+GW6471 group, silencing empty vector group, and sh-FNDC5 group. The mRNA and protein expression levels of FNDC5, PPARα, heme oxygenase-1, Bax, and Bcl-2 were detected by real-time PCR and western blot assay, respectively. Apoptosis of vascular smooth muscle cells was detected by flow cytometry and proliferation activity of vascular smooth muscle cells was detected by cell counting kit-8 assay.
RESULTS AND CONCLUSION: (1) Compared with the blank control group and overexpressed empty vector group, the expressions of FNDC5, PPARα, heme oxygenase-1, and Bax were increased, the expressions of Bcl-2 were decreased, and the ratio of Bax/Bcl-2 was increased in the FNDC5 group and FNDC5+GW6471 group (all P < 0.05). (2) Compared with the blank control group and silencing empty vector group, the expressions of FNDC5, PPARα, heme oxygenase-1, and Bax were decreased, the expressions of Bcl-2 were increased, and the ratio of Bax/Bcl-2 was decreased in the sh-FNDC5 group (all P < 0.05). (3) Compared with the FNDC5 group, the expressions of PPARα, heme oxygenase-1, and Bax were significantly decreased, Bcl-2 expression was increased, and Bax/Bcl-2 ratio was decreased in the FNDC5+GW6471 group (all P < 0.05). (4) Compared with the blank control group and overexpressed empty vector group, the proliferation activity of vascular smooth muscle cells was significantly decreased in the FNDC5 group and FNDC5+GW6471 group, while the apoptotic rate was significantly increased (all P < 0.05). (5) Compared with the blank control group and silencing empty vector group, the proliferation activity of vascular smooth muscle cells was increased in the sh-FNDC5 group, while the apoptotic rate was significantly decreased (both P < 0.05). (6) Compared with the FNDC5 group, the proliferation activity of vascular smooth muscle cells was significantly increased, while the apoptotic rate was significantly decreased in the FNDC5+GW6471 group (both P < 0.05). (7) Therefore, irisin/PPARα signaling pathway can inhibit proliferation activity and accelerate apoptosis of vascular smooth muscle cells by inducing heme oxygenase-1 expression.

Key words: irisin, peroxisome proliferator-activated receptor alpha, heme oxygenase-1, lentivirus vector, transfection, vascular smooth muscle cell, proliferation, apoptosis

CLC Number:

Wang Yao, Liu Danan, Zhao Guangjian, Zhou Bo, Wang Xiang. Irisin/peroxisome proliferator-activated receptor alpha signaling pathway mediates vascular smooth muscle cell proliferation in mice[J]. Chinese Journal of Tissue Engineering Research, 2023, 27(33): 5320-5326.

Figures/Tables 7

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