Prostaglandins & other lipid mediators · 2025
SREBF1 maintains the contractile phenotype of vascular smooth muscle cells via PPARγ signalling.
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Chen Xiaoying, Jin Huiling, Zheng Guanyi
Аннотация
BACKGROUND: Atherosclerosis is a complex chronic inflammatory disease. Although SREBF1 has been implicated in the regulation of atherosclerotic progression, its precise mechanisms remain incompletely understood.
METHODS: The study constructed an in vitro model of atherosclerosis by exposing vascular smooth muscle cells (VSMCs) to oxidized low-density lipoprotein. The model was validated through inverted microscopy, quantitative polymerase chain reaction, and western blotting. The effects of SREBF1 on VSMC's functions, including proliferation, migration, and clonogenic capacity, were assessed using Cell Counting Kit-8 assays, scratch wound healing assays, and colony formation assays, and western blotting following SREBF1 knockdown or overexpression. The PPARγ signalling pathway was further examined by western blotting and dual-luciferase reporter gene assay.
RESULTS: The experimental results demonstrated that knockdown of SREBF1 significantly enhanced VSMC proliferation and migration while suppressing the expression of the two contractile markers SM22α and α-SMA. Mechanistic studies revealed that SREBF1 directly upregulated PPARγ transcriptional activity, activated PPARγ expression, and inhibited phosphorylated PPARγ expression. Notably, the addition of GW9662, a specific PPARγ signalling inhibitor, partially reversed the regulatory effects of SREBF1 overexpression on VSMC proliferation, migration, and phenotype.
CONCLUSION: This research found that SREBF1 maintains the contractile phenotype of VSMCs by activating PPARγ signalling, suggesting that SREBF1 may serve as a key molecule in ameliorating atherosclerosis.
METHODS: The study constructed an in vitro model of atherosclerosis by exposing vascular smooth muscle cells (VSMCs) to oxidized low-density lipoprotein. The model was validated through inverted microscopy, quantitative polymerase chain reaction, and western blotting. The effects of SREBF1 on VSMC's functions, including proliferation, migration, and clonogenic capacity, were assessed using Cell Counting Kit-8 assays, scratch wound healing assays, and colony formation assays, and western blotting following SREBF1 knockdown or overexpression. The PPARγ signalling pathway was further examined by western blotting and dual-luciferase reporter gene assay.
RESULTS: The experimental results demonstrated that knockdown of SREBF1 significantly enhanced VSMC proliferation and migration while suppressing the expression of the two contractile markers SM22α and α-SMA. Mechanistic studies revealed that SREBF1 directly upregulated PPARγ transcriptional activity, activated PPARγ expression, and inhibited phosphorylated PPARγ expression. Notably, the addition of GW9662, a specific PPARγ signalling inhibitor, partially reversed the regulatory effects of SREBF1 overexpression on VSMC proliferation, migration, and phenotype.
CONCLUSION: This research found that SREBF1 maintains the contractile phenotype of VSMCs by activating PPARγ signalling, suggesting that SREBF1 may serve as a key molecule in ameliorating atherosclerosis.