Physical interaction of tropomyosin 3 and STIM1 regulates vascular smooth muscle contractility and contributes to hypertension.
Biomed Pharmacother
; 134: 111126, 2021 Feb.
Article
em En
| MEDLINE
| ID: mdl-33341060
ABSTRACT
SCOPE Tropomyosin (TPM), an actin-binding protein widely expressed across different cell types, is primarily involved in cellular contractile processes. We investigated whether TPM3 physically and functionally interacts with stromal interaction molecule 1 (STIM1) to contribute to vascular smooth muscle cell (VSMC) contraction, store-operated calcium entry (SOCE), and high-salt intake-induced hypertension in rats. METHODS AND RESULTS:
Analysis of a rat RNA-seq data set of 80 samples showed that the STIM1 and Tpm3 transcriptome expression pattern is highly correlated, and co-immunoprecipitation results indicated that TPM3 and STIM1 proteins physically interacted in rat VSMCs. Immunohistochemical data displayed obvious co-localization of TPM3 and STIM1 in rat VSMCs. Knockdown of TPM3 or STIM1 in VSMCs with specific small interfering RNA significantly suppressed contractions in tension measurement assays and decreased SOCE in calcium assays. Rats fed a high-salt diet for 4 weeks had significantly higher systolic blood pressure than controls, with significantly increased contractility and markedly increased TPM3 and STIM1 expression levels in the mesenteric resistance artery (shown by tension measurements and immunoblotting, respectively). Additionally, high salt environment in vitro induced significant enhancement of TPM3 and STIM1 expression levels in VSMCs.CONCLUSIONS:
We showed for the first time that TPM3 and STIM1 physically and functionally interact to contribute to VSMC contraction, SOCE, and high-salt intake-induced hypertension. Our findings provide mechanistic insights and offer a potential therapeutic target for high-salt intake-induced hypertension.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Tropomiosina
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Vasoconstrição
/
Pressão Sanguínea
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Miócitos de Músculo Liso
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Molécula 1 de Interação Estromal
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Hipertensão
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Músculo Liso Vascular
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article