Details

Autor(en) / Beteiligte

• Hu, Qiongying
• Li, Jinpeng
• Nitta, Kyoko
• Kitada, Munehiro
• Nagai, Takako
• Kanasaki, Keizo
• Koya, Daisuke

Titel

FGFR1 is essential for N-acetyl-seryl-aspartyl-lysyl-proline regulation of mitochondrial dynamics by upregulating microRNA let-7b-5p

Ist Teil von

• Biochemical and biophysical research communications, 2018-01, Vol.495 (3), p.2214-2220

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2018

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• Fibroblast growth factor receptor (FGFR) 1 plays a key role in endothelial homeostasis by inducing microRNA (miR) let-7. Our previous paper showed that anti-fibrotic effects of N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP) were associated with restoring diabetes-suppressed expression of FGFR1 and miR let-7, the key contributor of mitochondrial biogenesis, which is regulated by mitochondrial membrane GTPase proteins (MFN2 and OPA1). Here, we found that the FGFR1 signaling pathway was critical for AcSDKP in maintaining endothelial mitochondrial biogenesis through induction of miR let-7b-5p. In endothelial cells, AcSDKP restored the triple cytokines (TGF-β2, interleukin-1β, tumor necrosis factor-α)-suppressed miR let-7b-5p and protein levels of the mitochondrial membrane GTPase. This effect of AcSDKP was lost with either fibroblast growth factor receptor substrate 2 (FRS2) siRNA or neutralizing FGFR1-treated cells. Similarly, AcSDKP had no effect on the miR let-7b-5p inhibitor-suppressed GTPase levels in endothelial cells. In addition, a miR let-7b-5p mimic restored the levels of FRS2 siRNA-reduced GTPases in endothelial cells. These findings were also confirmed using MitoTracker Green and an immunofluorescence assay. Our results demonstrated that the AcSDKP-FGFR1 signaling pathway is critical for maintaining mitochondrial dynamics by control of miR let-7b-5p in endothelial cells. •FGFR1 signaling deficiency suppressed endothelial mitochondrial membrane GTPases and the miR let-7b-5p levels.•AcSDKP restored the protein levels of triple cytokines-suppressed endothelial mitochondrial membrane GTPases.•AcSDKP had no effect on mitochondrial dynamic in the FGFR1 signaling or miR let-7b-5p deficient cells.•miR let-7b-5p mimic restored the FGFR1 signaling deficiency-altered mitochondrial dynamics.