Researchers identified a novel mechanism by which fibroblast growth factor 21 (FGF21) decreases hypoxia-induced pulmonary arterial hypertension (PAH), as published in the Journal of Cellular and Molecular Medicine.
By inhibiting the negative regulatory effect of microRNA-130 (miR-130) on peroxisome proliferator-activated receptor gamma (PPARγ), this finding increases the understanding of the role of FGF21 in PAH and provides a new idea for the treatment of PAH, the authors said.
FGF21 is an endocrine hormone that has many biological functions. Recent research has shown that it can inhibit hypoxia-induced pulmonary artery smooth muscle cells proliferation and migration, which play a central role in the progression of PAH, by upregulating PPARγ.
This promotes programmed cell death and therefore downregulates inflammatory cytokine levels, improves collagen deposition in the lung, and reduces PAH.
Read more about PAH etiology
In the present study, a team of researchers from the First Affiliated Hospital of Wenzhou Medical University in Zhejiang, China found that FGF21 inhibited the elevation of miR-130 in hypoxia-induced PAH both in vitro and in vivo.
The team also showed that miR-130 reduces PPARγ expression and that inhibiting the expression of miR-130 suppressed the abnormal proliferation, migration, and resistance to apoptosis in hypoxic pulmonary artery smooth muscle cells. Knocking down PPARγ led to the corrections of this effect.
When the researchers exogenously administered miR-130 agomir, they saw an ameliorative effect of FGF21 on pulmonary vascular remodeling. Similarly, they observed an inhibitory effect on proliferation, migration, and apoptotic resistance in pulmonary artery smooth muscle cells.
“This study revealed the protective effect and mechanism of FGF21 on PAH through regulation of the miR-130/PPARγ axis, providing new ideas for the development of potential drugs for PAH based on FGF21,” they concluded.
Wang M, Su L, Sun J, et al. FGF21 attenuates pulmonary arterial hypertension via downregulation of miR-130, which targets PPARγ. J Cell Mol Med. Published online January 6, 2022. doi:10.1111/jcmm.17154