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蛋白激酶 Cα 通过激活细胞外信号调节激酶 1/2 通路刺激大鼠低氧诱导的肺动脉平滑肌细胞增殖。

Protein kinase Cα stimulates hypoxia‑induced pulmonary artery smooth muscle cell proliferation in rats through activating the extracellular signal‑regulated kinase 1/2 pathway.

机构信息

Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China.

Department of Respiratory and Critical Care Medicine, Shanxi Medical University Affiliated First Hospital, Taiyuan, Shanxi 030001, P.R. China.

出版信息

Mol Med Rep. 2017 Nov;16(5):6814-6820. doi: 10.3892/mmr.2017.7478. Epub 2017 Sep 12.

Abstract

Hypoxic pulmonary hypertension (HPH) may contribute to vascular remodeling, and pulmonary artery smooth muscle cell (PASMC) proliferation has an important role in this process. However, no relevant information concerning the role and mechanism of protein kinase C (PKC)α in hypoxia‑induced rat PASMC proliferation has been elucidated. The present study aimed to further investigate this by comparison of rat PASMC proliferation among normoxia for 72 h (21% O2), hypoxia for 72 h (3% O2), hypoxia + promoter 12‑myristate 13‑acetate control, hypoxia + safingol control, hypoxia + PD98059 control and hypoxia + U0126 control groups. The present study demonstrated that protein expression levels of PKCα in rat PASMCs were elevated. In conclusion, through activating the extracellular signal‑regulated 1/2 signaling pathway, PKCα is involved in and initiates PASMC proliferation, thus bringing about pulmonary artery hypertension. These results add to the understanding of the mechanism PKCα in PH formation and lays a theoretical basis for prevention as well as treatment of HPH.

摘要

低氧性肺动脉高压(HPH)可能导致血管重构,而肺动脉平滑肌细胞(PASMC)增殖在这一过程中起重要作用。然而,关于蛋白激酶 C(PKC)α在低氧诱导的大鼠 PASMC 增殖中的作用和机制尚不清楚。本研究通过比较常氧(21% O2)72 h、低氧(3% O2)72 h、低氧+12-肉豆蔻酸-13-醋酸盐对照组、低氧+鲨肝醇对照组、低氧+PD98059 对照组和低氧+U0126 对照组中大鼠 PASMC 增殖,进一步探讨了这一机制。本研究表明,大鼠 PASMC 中 PKCα的蛋白表达水平升高。综上所述,PKCα 通过激活细胞外信号调节激酶 1/2 信号通路,参与并启动 PASMC 增殖,从而导致肺动脉高压。这些结果增加了对 PH 形成中 PKCα 机制的理解,并为 HPH 的预防和治疗奠定了理论基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c3fa/5865839/9d6b1ec4a949/mmr-16-05-6814-g00.jpg

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