Substantial involvement of TRPM7 inhibition in the therapeutic effect of Ophiocordyceps sinensis on pulmonary hypertension.
Substantial involvement of TRPM7 inhibition in the therapeutic effect of Ophiocordyceps sinensis on pulmonary hypertension.
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DOI：
10.1016/j.trsl.2021.03.004
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发表时间：
2021-07
影响因子：
7.8
通讯作者：
Hirano, Katsuya
中科院分区：
文献类型：
--
作者：
Hiraishi, Keizo;Kurahara, Lin Hai;Feng, Jianlin;Yamamura, Aya;Cui, Yuanyuan;Yahiro, Eiji;Yokomise, Hiroyasu;Go, Tetsuhiko;Ishikawa, Kaori;Yokota, Naoya;Fujiwara, Atsushi;Onitsuka, Miki;Abe, Kohtaro;Ohga, Shoji;Satoh, Toru;Okada, Yasumasa;Yue, Lixia;Inoue, Ryuji;Hirano, Katsuya
中华眼镜蛇（Ophiocorphinensis，OCS）是一种昆虫病原真菌，具有抗增殖和抗组织重塑的作用。血管重构和血管收缩在肺动脉高压（PH）的发生发展中起关键作用。使用啮齿动物PH模型和培养的肺动脉内皮细胞和平滑肌细胞（PAEC和PASMC）研究OCS对PH的治疗潜力，重点是TRPM 7的参与。OCS可明显改善肺高压大鼠的肺高压发生、右心室肥厚及功能障碍。TRPM 7基因敲除可减弱野百合碱吡咯诱导的PH小鼠的PH发展。TRPM 7与PH大鼠和人类的中膜肥大和丛状病变有关。OCS抑制来自PH患者的PASMCs的增殖。OCS乙醇提取物抑制PAEC或PASMCs中TRPM 7样电流、TGF-β2诱导的内皮-间质转化、IL-6诱导的STAT 3磷酸化和PDGF诱导的Akt磷酸化。这些抑制作用通过siRNA介导的TRPM 7敲低或用TRPM 7拮抗剂FTY-720处理来重现。OCS和FTY-720在离体正常人肺动脉中诱导血管舒张。因此，本研究提出了OCS治疗PH的治疗潜力。抑制TRPM 7被认为是OCS治疗作用的基础。
Ophiocordyceps sinensis (OCS), an entomopathogenic fungus, is known to exert antiproliferative and antitissue remodeling effects. Vascular remodeling and vasoconstriction play critical roles in the development of pulmonary hypertension (PH). The therapeutic potential of OCS for PH was investigated using rodent PH models, and cultured pulmonary artery endothelial and smooth muscle cells (PAECs and PASMCs), with a focus on the involvement of TRPM7. OCS ameliorated the development of PH, right ventricular hypertrophy and dysfunction in the monocrotaline-induced PH rats. The genetic knockout of TRPM7 attenuated the development of PH in mice with monocrotaline pyrrole-induced PH. TRPM7 was associated with medial hypertrophy and the plexiform lesions in rats and humans with PH. OCS suppressed proliferation of PASMCs derived from the PH patients. Ethanol extracts of OCS inhibited TRPM7-like current, TGF-β2-induced endothelial-mesenchymal transition, IL-6-induced STAT3 phosphorylation, and PDGF-induced Akt phosphorylation in PAECs or PASMCs. These inhibitory effects were recapitulated by either siRNA-mediated TRPM7 knockdown or treatment with TRPM7 antagonist FTY-720. OCS and FTY-720 induced vasorelaxation in the isolated normal human pulmonary artery. As a result, the present study proposes the therapeutic potential of OCS for the treatment of PH. The inhibition of TRPM7 is suggested to underlie the therapeutic effect of OCS.
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影响因子：
4.6
作者：
Huang TT;Lai HC;Ko YF;Ojcius DM;Lan YW;Martel J;Young JD;Chong KY
通讯作者：
Chong KY
影响因子：
4.8
作者：
Liu M;Inoue K;Leng T;Guo S;Xiong ZG
通讯作者：
Xiong ZG
DOI：
10.5339/gcsp.2014.29
发表时间：
2014
期刊：
Global cardiology science & practice
影响因子：
--
作者：
Chester AH;Yacoub MH
通讯作者：
Yacoub MH
影响因子：
3.6
作者：
Paugh, Steven W.;Cassidy, Michael P.;Selley, Dana E.
通讯作者：
Selley, Dana E.
影响因子：
6.1
作者：
Chen, YJ;Shiao, MS;Wang, SY
通讯作者：
Wang, SY