Fibroblast growth factor 10 protects neuron against oxygen–glucose deprivation injury through inducing heme oxygenase-1

• Published in: Biochemical and biophysical research communications Vol. 456; no. 1; pp. 225 - 231
• Main Authors: Li, Yong-Hua, Yang, Li-Ye, Chen, Wei, Li, Ying-Ke, Yuan, Hong-Bin
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 02.01.2015
• Subjects: 60 APPLIED LIFE SCIENCES; AMP; ANGIOGENESIS; Animals; ANOXIA; APOPTOSIS; BIOLOGICAL FUNCTIONS; Blood Glucose - metabolism; Brain Ischemia - pathology; CELL PROLIFERATION; Cell Survival; Cells, Cultured; Cerebral Cortex - metabolism; Cerebral ischemia; Extracellular Signal-Regulated MAP Kinases - metabolism; FGF10; Fibroblast Growth Factor 10 - metabolism; FIBROBLASTS; Flow Cytometry; GLUCOSE; GROWTH FACTORS; HEME; Heme Oxygenase-1 - metabolism; HEPARIN; HO-1; Humans; Immunohistochemistry; ISCHEMIA; Male; Membrane Proteins - metabolism; MICE; Mice, Inbred C57BL; NERVE CELLS; Neurons - metabolism; Neuroprotection; OXYGEN; Oxygen - metabolism; PC12 Cells; PHOSPHOTRANSFERASES; Rats; Reactive Oxygen Species - metabolism; RNA, Small Interfering - metabolism; Stroke - pathology; VIABILITY; Neuroprotection; Cerebral ischemia; HO-1; FGF10
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2014.11.063

•FGF10 attenuates OGD induced injury in cortical neuron.•FGF10 reduces OGD triggered ROS level in cortical neuron.•FGF10 induces HO-1 expression upon OGD stimuli in cortical neuron.•Knockdown of HO-1 impairs the neuroprotection of FGF10 in OGD model. Fibroblast growth factors (FGFs) are a family of structurally related heparin-binding proteins with diverse biological functions. FGFs participate in mitogenesis, angiogenesis, cell proliferation, development, differentiation and cell migration. Here, we investigated the potential effect of FGF10, a member of FGFs, on neuron survival in oxygen–glucose deprivation (OGD) model. In primary cultured mouse cortical neurons upon OGD, FGF10 treatment (100 and 1000ng/ml) attenuated the decrease of cell viability and rescued the LDH release. Tuj-1 immunocytochemistry assay showed that FGF10 promoted neuronal survival. Apoptosis assay with Annexin V+PI by flow cytometry demonstrated that FGF10 treatment reduced apoptotic cell proportion. Moreover, immunoblotting showed that FGF10 alleviated the cleaved caspase-3 upregulation caused by OGD. FGF10 treatment also depressed the OGD-induced increase of caspase-3, -8 and -9 activities. At last, we found FGF10 triggered heme oxygenase-1 (HO-1) protein expression rather than hypoxia-inducible factor-1 (HIF-1), AMP-activated protein kinase (AMPK) signaling and extracellular signal-regulated kinases 1/2 (ERK1/2) signaling. Knockdown of HO-1 by siRNA partly abolished the neuroprotection of FGF10 in OGD model. In summary, our observations provide the first evidence for the neuroprotective function of FGF10 against ischemic neuronal injury and suggest that FGF10 may be a promising agent for treatment of ischemic stroke.