淫羊藿苷通过雌激素受体α-p38丝裂原活化蛋白激酶途径减轻血管平滑肌细胞钙化。
Icariin attenuates the calcification of vascular smooth muscle cells through ERα - p38MAPK pathway.
作者信息
He Jieyu, Wang Yanjiao, Zhan Junkun, Li Shuang, Ni Yuqing, Huang Wu, Long Limin, Tan Pan, Wang Yi, Liu Youshuo
机构信息
Department of Geriatrics, The Second Xiangya Hospital Central South University Changsha China.
出版信息
Aging Med (Milton). 2023 Oct 10;6(4):379-385. doi: 10.1002/agm2.12267. eCollection 2023 Dec.
OBJECTIVE
To investigate the relationship between icariin and the osteoblastic differentiation of vascular smooth muscle cells (VSMCs) and the signal pathway involved.
METHODS
We applied a universally accepted calcification model of VSMCs induced by β glycerophosphate. Then the VSMCs calcification was observed by treatment with icariin and/or inhibitors of estrogen receptors (ERs) and p38-mitogen-activated protein kinase (MAPK) signaling.
RESULTS
Icariin inhibited osteoblastic differentiation and mineralization of VSMCs due to decreased ALP activity and Runx2 expression. Further study demonstrated that icariin exerted this suppression effect through activating p38-MAPK but not extracellular-regulated kinase, JNK or Akt. An inhibitor of p38-MAPK partially reversed the inhibitory effects of icariin on osteoblastic differentiation. Interestingly, treatment of VSMCs with an ER antagonist ICI182780 and a selective ERα receptor antagonist PPT attenuated icariin-mediated inhibition effect of VSMCs calcification, associated with suppression of p38-MAPK phosphorylation.
CONCLUSIONS
Icariin inhibited the osteoblastic differentiation of VSMCs, and that the inhibitory effects were mediated by p38-MAPK pathways through ERα.
目的
探讨淫羊藿苷与血管平滑肌细胞（VSMCs）成骨分化之间的关系及相关信号通路。
方法
应用β-甘油磷酸诱导的VSMCs普遍接受的钙化模型。然后用淫羊藿苷和/或雌激素受体（ERs）及p38丝裂原活化蛋白激酶（MAPK）信号抑制剂处理观察VSMCs钙化情况。
结果
淫羊藿苷由于碱性磷酸酶（ALP）活性和Runx2表达降低而抑制VSMCs的成骨分化和矿化。进一步研究表明，淫羊藿苷通过激活p38-MAPK而非细胞外调节激酶、JNK或Akt发挥这种抑制作用。p38-MAPK抑制剂部分逆转了淫羊藿苷对成骨分化的抑制作用。有趣的是，用ER拮抗剂ICI182780和选择性ERα受体拮抗剂PPT处理VSMCs减弱了淫羊藿苷介导的VSMCs钙化抑制作用，这与p38-MAPK磷酸化的抑制有关。
结论
淫羊藿苷抑制VSMCs的成骨分化，且抑制作用是通过ERα经p38-MAPK途径介导的。
Zotero 插件