Lactate promotes vascular smooth muscle cell switch to a synthetic phenotype by inhibiting miR-23b expression

• 영문명: Lactate promotes vascular smooth muscle cell switch to a synthetic phenotype by inhibiting miR-23b expression
• 발행기관: 대한생리학회-대한약리학회
• 저자명: Yanchao Hu Chunyan Zhang Yajie Fan Yan Zhang Yiwen Wang Congxia Wang
• 간행물 정보: 『The Korean Journal of Physiology & Pharmacology』제26권 제6호, 519~530쪽, 전체 12쪽
• 주제분류: 의약학 > 의학일반
• 파일형태: PDF
• 발행일자: 2022.11.30

영문 초록

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.

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키워드

Lactate miR-23b Phenotype switch SMAD3 Smooth muscle