Fibroblast growth factor receptor-1 is essential for regulation of mitochondrial biogenesis via control of microRNA let-7b
10.3760/cma.j.issn.1000-6699.2018.05.009
- VernacularTitle:成纤维生长因子受体1通过控制微小RNA let-7 b表达调节内皮细胞线粒体生源的作用研究
- Author:
Qiongying HU
1
;
Jiao YANG
;
Gaolin CHEN
;
Qiu CEN
Author Information
1. 610072,成都中医药大学附属医院检验科
- Keywords:
FGFR1;
FRS2;
Mitochondrial biogenesis;
MicroRNA let-7b-5p
- From:
Chinese Journal of Endocrinology and Metabolism
2018;34(5):404-409
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the role of fibroblast growth factor receptor ( FGFR ) 1 in endothelial homeostasis via an induction of microRNA let-7s, with effects on AcSDKP(N-acetyl-seryl-aspartyl-lysyl-proline) and associated mitochondrial biogenesis. Methods Blocking FGFR1 signaling pathway, Western blot and immunofluorescence staining were used to measure mitochondrial fusion ( mitofusin-2, MFN2;optic atrophy protein 1, OPA1 ) and fission ( dynamin-related protein-1, DRP1 ) proteins and mitochondrial biogenesis by MitoTraker Green. Also real-time quantitative PCR(qPCR) was performed to test microRNA let-7' expression. Results FGFR1 signaling pathway was critical for AcSDKP maintaining mitochondrial biogenesis through induction of microRNA let-7b. In endothelial cells, the AcSDKP restored the triple[TGF-β2, interleukin (IL)-1β, tumor necrosis factor (TNF)-α]-suppressed microRNA let-7b-5p expression and associated with mitochondrial biogenesis. Such effect of AcSDKP was lost in either fibroblast growth factor receptor substrate 2 (FRS2) siRNA or neutralizing FGFR1 treated-cells. Similarly, AcSDKP lost its effect on mitochondrial biogenesis in microRNA let-7b-5p inhibitor-treated-cells. In addition, microRNA let-7b-5p mimic reversed the FRS2 siRNA-suppressed mitochondrial biogenesis in endothelial cells. Conclusion These findings demonstrated that FGFR1 is critical for maintaining mitochondrial biogenesis through control of microRNA let-7b-5p in endothelial cells.
