title: Fibroblast growth factor 10 protects neuron against oxygen-glucose deprivation injury through inducing heme oxygenase-1.
abstract: 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 1000 ng/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.
authors.affiliation: Department of Anesthesiology, Changzheng Hospital, 415 Fengyang Road, Second Military Medical University, Shanghai, China.
authors.forename: Yong-Hua
authors.initials: YH
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, Changzheng Hospital, 415 Fengyang Road, Second Military Medical University, Shanghai, China.
authors.forename: Li-Ye
authors.initials: LY
authors.lastname: Yang
authors.affiliation: Department of Anesthesiology, Changzheng Hospital, 415 Fengyang Road, Second Military Medical University, Shanghai, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Anesthesiology, Changzheng Hospital, 415 Fengyang Road, Second Military Medical University, Shanghai, China. Electronic address: liyingke6f@126.com.
authors.forename: Ying-Ke
authors.initials: YK
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, Changzheng Hospital, 415 Fengyang Road, Second Military Medical University, Shanghai, China. Electronic address: yuanhongbin6f@126.com.
authors.forename: Hong-Bin
authors.initials: HB
authors.lastname: Yuan
mesh_terms: D000818:Animals; D017209:Apoptosis; D001786:Blood Glucose / Q000378:metabolism*; D002545:Brain Ischemia / Q000473:pathology; D049109:Cell Proliferation; D002470:Cell Survival; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D051526:Fibroblast Growth Factor 10 / Q000378:metabolism*; D005434:Flow Cytometry; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism*; D016716:PC12 Cells; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D020521:Stroke / Q000473:pathology
chemical_list: D001786:Blood Glucose; C496463:FGF10 protein, human; D051526:Fibroblast Growth Factor 10; D008565:Membrane Proteins; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse; D048049:Extracellular Signal-Regulated MAP Kinases; D010100:Oxygen
keywords: Cerebral ischemia; FGF10; HO-1; Neuroprotection