FGF21 attenuates hypoxia-induced dysfunction and inflammation in HPAECs via the microRNA-27b-mediated PPARγ pathway
FGF21 attenuates hypoxia-induced dysfunction and inflammation in HPAECs via the microRNA-27b-mediated PPARγ pathway
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FGF21 通过 microRNA-27b 介导的 PPAR gamma 途径减轻缺氧引起的 HPAEC 功能障碍和炎症
DOI：
10.3892/ijmm.2021.4949
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发表时间：
2021-06-01
影响因子：
5.4
通讯作者：
Huang, Xiaoying
中科院分区：
文献类型：
--
作者：
Yao, Dan;He, Qinlian;Huang, Xiaoying
肺动脉高压（PAH）是一种慢性进行性疾病，其特征是肺血管重构，包括内皮细胞功能障碍和炎症。microRNAs（miRNAs或miRs）在PAH的发生发展中起重要作用。此外，已发现成纤维细胞生长因子21（FGF 21）具有显著的抗功能障碍和抗炎特性。因此，本研究旨在研究FGF 21通过miR-27 b/过氧化物酶体增殖物激活受体γ（PPAR γ）轴对PAH的潜在作用。采用缺氧的人肺动脉内皮细胞（HPAECs）作为PAH模型。结果显示，缺氧后HPAECs中PPAR γ表达下调，miR-27 b表达上调。荧光素酶检测表明，PPAR γ是miR-27 b的靶基因。此外，miR-27 b抑制了PPAR γ基因的表达，从而加重了缺氧诱导的HPAEC功能障碍。此外，miR-27 B通过靶向PPAR γ激活核因子-κ B信号通路和炎症因子[白细胞介素（IL）-1 β、IL-6和肿瘤坏死因子-α]的表达。此外，用FGF 21处理缺氧暴露的HPAEC后，miR-27 b的表达降低。此外，FGF 21通过抑制miR-27 b表达从而促进PPAR γ表达来减轻缺氧诱导的HPAEC功能障碍和炎症。总的来说，本研究的结果表明，FGF 21可以作为通过miR-27 b介导的PPAR γ途径管理PAH的治疗靶点。
Pulmonary arterial hypertension (PAH), is a chronic and progressive disorder characterized by pulmonary vascular remodeling, including endothelial cell dysfunction and inflammation. MicroRNAs (miRNAs or miRs) play an important role in the development of PAH. In addition, fibroblast growth factor 21 (FGF21) has been found to have marked anti-dysfunction and anti-inflammatory properties. Therefore, the present study aimed to investigate the latent effects of FGF21 against PAH through the miR-27b/peroxisome proliferator-activated receptor gamma (PPAR gamma) axis. Human pulmonary arterial endothelial cells (HPAECs) subjected to hypoxia were used as PAH models. The results revealed that PPAR gamma expression was downregulated and miR-27b expression was upregulated in the HPAECs exposed to hypoxia. Luciferase assay suggested that PPAR gamma was a target gene of miR-27b. Furthermore, miR-27b inhibited the expression of the PPAR gamma gene, thereby aggravating hypoxia-induced HPAEC dysfunction. Moreover, miR-27b activated the nuclear factor-kappa B signaling pathway and the expression of inflammatory factors [interleukin (IL)-1 beta, IL-6 and tumor necrosis factor-alpha] by targeting PPAR gamma. In addition, the expression of miR-27b decreased following treatment of the hypoxia-exposed HPAECs with FGF21. Furthermore, FGF21 alleviated hypoxia-induced HPAEC dysfunction and inflammation by inhibiting miR-27b expression and thereby promoting PPAR gamma expression. On the whole, the findings of the present study suggest that FGF21 may serve as a therapeutic target for managing PAH through the miR-27b-mediated PPAR gamma pathway.