FGF21 attenuates hypoxia‑induced dysfunction and inflammation in HPAECs via the microRNA‑27b‑mediated PPARγ pathway

Yao,Dan; He,Qinlian; Sun,Junwei; Cai,Luqiong; Wei,Jinqiu; Cai,Gexiang; Liu,Jingjing; Lin,Yinuo; Wang,Liangxing; Huang,Xiaoying

doi:10.3892/ijmm.2021.4949

FGF21 attenuates hypoxia‑induced dysfunction and inflammation in HPAECs via the microRNA‑27b‑mediated PPARγ pathway

Authors:
- Dan Yao
- Qinlian He
- Junwei Sun
- Luqiong Cai
- Jinqiu Wei
- Gexiang Cai
- Jingjing Liu
- Yinuo Lin
- Liangxing Wang
- Xiaoying Huang
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Affiliations: Division of Pulmonary Medicine, The First Affiliated Hospital of Wenzhou Medical University, Key Laboratory of Heart and Lung, Wenzhou, Zhejiang 325000, P.R. China
Published online on: April 27, 2021 https://doi.org/10.3892/ijmm.2021.4949
Article Number: 116
Copyright: © Yao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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 γ (PPARγ) axis. Human pulmonary arterial endothelial cells (HPAECs) subjected to hypoxia were used as PAH models. The results revealed that PPARγ expression was downregulated and miR‑27b expression was upregulated in the HPAECs exposed to hypoxia. Luciferase assay suggested that PPARγ was a target gene of miR‑27b. Furthermore, miR‑27b inhibited the expression of the PPARγ gene, thereby aggravating hypoxia‑induced HPAEC dysfunction. Moreover, miR‑27b activated the nuclear factor‑κB signaling pathway and the expression of inflammatory factors [interleukin (IL)‑1β, IL‑6 and tumor necrosis factor‑α] by targeting PPARγ. 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 PPARγ 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 PPARγ pathway.

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