Elabela prevents angiotensin II-induced apoptosis and inflammation in rat aortic adventitial fibroblasts via the activation of FGF21-ACE2 signaling.
Elabela prevents angiotensin II-induced apoptosis and inflammation in rat aortic adventitial fibroblasts via the activation of FGF21-ACE2 signaling.
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Elabela 通过激活 FGF21-ACE2 信号传导防止血管紧张素 II 诱导的大鼠主动脉外膜成纤维细胞凋亡和炎症
DOI：
10.1007/s10735-021-10011-3
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发表时间：
2021-10
影响因子：
3.2
通讯作者：
Zhong JC
中科院分区：
文献类型：
--
作者：
Song JJ;Yang M;Liu Y;Song JW;Liu XY;Miao R;Zhang ZZ;Liu Y;Fan YF;Zhang Q;Dong Y;Yang XC;Zhong JC
细胞凋亡、炎症和纤维化导致血管重塑和损伤。Elabela（ELA）是维持血管功能的重要调节因子，参与高血压血管重构的发病机制。本研究旨在探讨ELA对血管紧张素II（ATII）诱导的大鼠主动脉外膜成纤维细胞（AF）的调节作用及其机制。在培养的AF中，暴露于ATII导致ELA、成纤维细胞生长因子21（FGF 21）和血管紧张素转换酶2（ACE 2）的mRNA和蛋白水平显著降低，以及凋亡、炎症、氧化应激和细胞迁移增加，这些分别被ELA和重组FGF 21的外源性补充部分阻断。此外，ELA治疗显著逆转了ATII介导的大鼠主动脉AF中FGF 21和ACE 2水平的丧失。FGF 21敲低与小干扰RNA（siRNA）显着抵消ELA对ATII介导的促进大鼠主动脉AF细胞迁移，凋亡，炎症和氧化损伤的保护作用。更重要的是，预处理与重组FGF 21显着抑制ATII介导的ACE 2的损失和细胞凋亡，氧化应激和炎症损伤的增加，在大鼠主动脉AF，这是部分防止敲低ACE 2与siRNA。总之，ELA通过激活FGF 21-ACE 2信号传导在大鼠主动脉AF中发挥其抗凋亡、抗炎和抗氧化作用。ELA可能代表预测血管损伤的潜在候选者，并且靶向FGF 21-ACE 2信号传导可能是血管外膜重塑和相关疾病的有希望的治疗干预。
Apoptosis, inflammation, and fibrosis contribute to vascular remodeling and injury. Elabela (ELA) serves as a crucial regulator to maintain vascular function and has been implicated in the pathogenesis of hypertensive vascular remodeling. This study aims to explore regulatory roles and underlying mechanisms of ELA in rat aortic adventitial fibroblasts (AFs) in response to angiotensin II (ATII). In cultured AFs, exposure to ATII resulted in marked decreases in mRNA and protein levels of ELA, fibroblast growth factor 21 (FGF21), and angiotensin-converting enzyme 2 (ACE2) as well as increases in apoptosis, inflammation, oxidative stress, and cellular migration, which were partially blocked by the exogenous replenishment of ELA and recombinant FGF21, respectively. Moreover, treatment with ELA strikingly reversed ATII-mediated the loss of FGF21 and ACE2 levels in rat aortic AFs. FGF21 knockdown with small interfering RNA (siRNA) significantly counterbalanced protective effects of ELA on ATII-mediated the promotion of cell migration, apoptosis, inflammatory, and oxidative injury in rat aortic AFs. More importantly, pretreatment with recombinant FGF21 strikingly inhibited ATII-mediated the loss of ACE2 and the augmentation of cell apoptosis, oxidative stress, and inflammatory injury in rat aortic AFs, which were partially prevented by the knockdown of ACE2 with siRNA. In summary, ELA exerts its anti-apoptotic, anti-inflammatory, and anti-oxidant effects in rat aortic AFs via activation of the FGF21–ACE2 signaling. ELA may represent a potential candidate to predict vascular damage and targeting the FGF21–ACE2 signaling may be a promising therapeutic intervention for vascular adventitial remodeling and related disorders.
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影响因子：
29
作者：
Pan, Xuebo;Shao, Yihui;Lin, Zhuofeng
通讯作者：
Lin, Zhuofeng
血管紧张素转换酶 2 激活通过介导内皮一氧化氮合酶的磷酸化改善肺动脉高压大鼠的肺内皮功能障碍
DOI：
10.1016/j.jash.2017.10.009
发表时间：
2017-12-01
影响因子：
--
作者：
Li, Gang;Zhang, Han;Liu, Yinglong
通讯作者：
Liu, Yinglong
影响因子：
37.8
作者：
Lin Z;Pan X;Wu F;Ye D;Zhang Y;Wang Y;Jin L;Lian Q;Huang Y;Ding H;Triggle C;Wang K;Li X;Xu A
通讯作者：
Xu A
影响因子：
4.6
作者：
Wang Z;Yu D;Wang M;Wang Q;Kouznetsova J;Yang R;Qian K;Wu W;Shuldiner A;Sztalryd C;Zou M;Zheng W;Gong DW
通讯作者：
Gong DW
DOI：
10.1161/hypertensionaha.115.06262
发表时间：
2016-05
期刊：
Hypertension (Dallas, Tex. : 1979)
影响因子：
--
作者：
Bersi MR;Bellini C;Wu J;Montaniel KRC;Harrison DG;Humphrey JD
通讯作者：
Humphrey JD