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[m-Nisodipine inhibited 5-HT-induced proliferation of rat PASMCs through Rho/ROCK signal pathway]

Huan-long Liu, Ding Yu, Zhong-ning Zhu

    Yao Xue Xue Bao = Acta Pharmaceutica Sinica
    |November 11, 2015
    PubMed

    Insights

    This study reveals the Rho/ROCK pathway is crucial for 5-HT-induced pulmonary artery smooth muscle cell proliferation. M-nis effectively inhibits this proliferation by blocking the Rho/ROCK pathway.

    Area of Science:

    • Cell Biology
    • Pharmacology
    • Physiology

    Background:

    • Pulmonary artery smooth muscle cells (PASMCs) proliferation is implicated in pulmonary hypertension.
    • The Rho/ROCK signaling pathway is known to regulate vascular tone and cell growth.
    • 5-hydroxytryptamine (5-HT) is a vasoactive substance that can influence PASMC behavior.

    Purpose of the Study:

    • To investigate the role of the Rho/ROCK signaling pathway in 5-HT-induced PASMC proliferation.
    • To examine the inhibitory effect of m-Nis on this pathway and subsequent cell proliferation.

    Main Methods:

    • PASMCs were cultured using the explant technique.
    • MTT assay was employed to quantify cell proliferation.
    • RT-PCR and Western blot analyses were performed to assess gene and protein expression (RhoA, ROCK1, p-MYPT1).

    Main Results:

    • 5-HT significantly induced PASMC proliferation over 12-72 hours.
    • M-nis demonstrated a dose-dependent inhibition of 5-HT-induced PASMC proliferation.
    • M-nis also inhibited the mRNA expression of RhoA and ROCK1, and the protein expression of p-MYPT1.

    Conclusions:

    • The Rho/ROCK pathway is a key mediator of 5-HT-induced PASMC proliferation.
    • M-nis exhibits significant inhibitory effects on PASMC proliferation, likely through the blockade of the Rho/ROCK signaling pathway.
    • These findings suggest potential therapeutic implications for conditions involving PASMC hyperproliferation.

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