Lactate promotes vascular smooth muscle cell switch to a synthetic phenotype by inhibiting miR-23b expression
10.4196/kjpp.2022.26.6.519
- Author:
Yanchao HU
1
;
Chunyan ZHANG
;
Yajie FAN
;
Yan ZHANG
;
Yiwen WANG
;
Congxia WANG
Author Information
1. Department of Cardiovascular Medicine, The Second Affiliated Hospital of Xi'an Jiaotong University, Shaanxi 710004, China
- Publication Type:Original Article
- From:The Korean Journal of Physiology and Pharmacology
2022;26(6):519-530
- CountryRepublic of Korea
- Language:English
-
Abstract:
Recent research indicates that lactate promotes the switching of vascular smooth muscle cells (VSMCs) to a synthetic phenotype, which has been implicated in various vascular diseases. This study aimed to investigate the effects of lactate on the VSMC phenotype switch and the underlying mechanism. The CCK-8 method was used to assess cell viability. The microRNAs and mRNAs levels were evaluated using quantitative PCR. Targets of microRNA were predicted using online tools and confirmed using a luciferase reporter assay. We found that lactate promoted the switch of VSMCs to a synthetic phenotype, as evidenced by an increase in VSMC proliferation, mitochondrial activity, migration, and synthesis but a decrease in VSMC apoptosis. Lactate inhibited miR-23b expression in VSMCs, and miR-23b inhibited VSMC's switch to the synthetic phenotype. Lactate modulated the VSMC phenotype through downregulation of miR-23b expression, suggesting that overexpression of miR-23b using a miR-23b mimic attenuated the effects of lactate on VSMC phenotype modulation. Moreover, we discovered that SMAD family member 3 (SMAD3) was the target of miR-23b in regulating VSMC phenotype. Further findings suggested that lactate promotes VSMC switch to synthetic phenotype by targeting SMAD3 and downregulating miR-23b. These findings suggest that correcting the dysregulation of miR-23b/ SMAD3 or lactate metabolism is a potential treatment for vascular diseases.
