1. 17β-estradiol reduces NF-κB expression induced by increased crosstalk between KLF5 and ERα in murine vascular smooth muscle cells.
- Author
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Zhang, Man-li, Zhang, Man-na, Wang, Wen-li, Chen, Hui, Wang, Xia, Li, Xuan, Li, Li, and Tong, Fei
- Subjects
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VASCULAR smooth muscle , *MUSCLE cells , *VASCULAR remodeling , *CARDIOVASCULAR system - Abstract
Pathological vascular remodeling and cell proliferation play vital roles in many proliferative vascular diseases. Estrogen can protect the cardiovascular system, but its exact molecular mechanism is unknown. Here we report that 17β-estradiol (E2) suppressed vascular smooth muscle cells (VSMCs) proliferation and inflammation. qRT-PCR and Western blot demonstrated that E2 decreased NF-κB p50 expression and reduced VSMCs proliferation and inflammation. Mechanistically, a dual luciferase reporter assay and chromatin immunoprecipitation suggested that KLF5 promoted NF-κB p50 expression by binding to the NF-κB p50 promoter, whereas E2 reduced the effect of KLF5 binding to the NF-κB p50 promoter and inhibited NF-κB p50 expression. Furthermore, a coimmunoprecipitation assay and immunofluorescence staining showed that the interaction between KLF5 and ERα increased in VSMCs treated with E2, which in turn decreased NF-κB p50 expression levels. Altogether, we reveal that E2 inhibits VSMCs proliferation and inflammation by reducing NF-κB expression induced by an increased interaction between KLF5 and ERα. These data provide further insights into how E2 inhibits vascular proliferation and inflammation. • 17β-estradiol (E2) inhibits VSMCs proliferation and inflammation in vivo and in vitro. • E2 inhibits NF-κB p50 expression and reduced proliferation and inflammation of VSMCs and vascular intimal. • E2 reduces NF-κB p50 expression via KLF5 regulating NF-κB p50 promoter. • The interaction between ERα and KLF5 increases in the presence of E2, then decreases NF-κB p50 expression. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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