|
KMID : 0620920190510020017
|
|
Experimental & Molecular Medicine
2019 Volume.51 No. 2 p.17 ~ p.17
|
|
|
NF-κB-responsive miR-155 induces functional impairment of vascular smooth muscle cells by downregulating soluble guanylyl cyclase
|
|
Park Min-Sik
Choi Seung-Hwan
Kim Su-Ji
Kim Joo-Hwan
Lee Dong-Keon
Park Won-Jin
Kim Tae-Sam
Jung Ji-Won
Hwang Jong-Yun
Won Moo-Ho
Ryoo Sung-Woo
Kang Seung-Goo
Ha Kwon-Soo
Kwon Young-Guen
Kim Young-Myeong
|
|
|
Abstract
|
|
|
|
Vascular smooth muscle cells (VSMCs) play an important role in maintaining vascular function. Inflammation-mediated VSMC dysfunction leads to atherosclerotic intimal hyperplasia and preeclamptic hypertension; however, the underlying mechanisms are not clearly understood. We analyzed the expression levels of microRNA-155 (miR-155) in cultured VSMCs, mouse vessels, and clinical specimens and then assessed its role in VSMC function. Treatment with tumor necrosis factor-α (TNF-α) elevated miR-155 biogenesis in cultured VSMCs and vessel segments, which was prevented by NF-κB inhibition. MiR-155 expression was also increased in high-fat diet-fed ApoE?/? mice and in patients with atherosclerosis and preeclampsia. The miR-155 levels were inversely correlated with soluble guanylyl cyclase β1 (sGCβ1) expression and nitric oxide (NO)-dependent cGMP production through targeting the sGCβ1 transcript. TNF-α-induced miR-155 caused VSMC phenotypic switching, which was confirmed by the downregulation of VSMC-specific marker genes, suppression of cell proliferation and migration, alterations in cell morphology, and NO-induced vasorelaxation. These events were mitigated by miR-155 inhibition. Moreover, TNF-α did not cause VSMC phenotypic modulation and limit NO-induced vasodilation in aortic vessels of miR-155?/? mice. These findings suggest that NF-κB-induced miR-155 impairs the VSMC contractile phenotype and NO-mediated vasorelaxation by downregulating sGCβ1 expression. These data suggest that NF-κB-responsive miR-155 is a novel negative regulator of VSMC functions by impairing the sGC/cGMP pathway, which is essential for maintaining the VSMC contractile phenotype and vasorelaxation, offering a new therapeutic target for the treatment of atherosclerosis and preeclampsia.
|
|
|
KEYWORD
|
|
|
Cell migration, Disease model, RNAi
|
|
|
FullTexts / Linksout information
|
|
|
|
|
Listed journal information
|
|
    
|