rhFGF20 promotes angiogenesis and vascular repair following traumatic brain injury by regulating Wnt/β-catenin pathway - 09/10/21
, Li Lin a, b, c, ⁎ Bienvenue sur EM-consulte, la référence des professionnels de santé.
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Abstract |
The pathology of cerebrovascular disorders takes an important role in traumatic brain injury (TBI) by increasing intracranial pressure. Fibroblast growth factor 20 (FGF20) is a brain-derived neurotrophic factor, that has been shown to play an important role in the survival of dopaminergic neurons and the treatment of Parkinson's disease (PD). However, little is known about the role of FGF20 in the treatment of TBI and its underlying mechanism. The purpose of this study was to evaluate the protective effect of recombinant human FGF20 (rhFGF20) on protecting cerebral blood vessels after TBI. In this study, we indicated that rhFGF20 could reduce brain edema, Evans blue penetration and upregulated the expression of blood-brain barrier (BBB)-related tight junction (TJ) proteins, exerting a protective effect on the BBB in vivo after TBI. In the TBI repair phase, rhFGF20 promoted angiogenesis, neurological and cognitive function recovery. In tumor necrosis factor-α (TNF-α)-induced human brain microvascular endothelial cells (hCMEC/D3), an in vitro BBB disruption model, rhFGF20 reversed the impairment in cell migration and tube formation induced by TNF-α. Moreover, in both the TBI mouse model and the in vitro model, rhFGF20 increased the expression of β-catenin and GSK3β, which are the two key regulators in the Wnt/β-catenin signaling pathway. In addition, the Wnt/β-catenin inhibitor IWR-1-endo significantly reversed the effects of rhFGF20. These results indicate that rhFGF20 may prevent vascular repair and angiogenesis through the Wnt/β-catenin pathway.
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Highlights |
• | rhFGF20 treatment improves the neurological function, learning and memory behaviors of mice after TBI. |
• | rhFGF20 upregulates TJ and AJ protein expression and rescues BBB disruption after TBI. |
• | rhFGF20 enhances angiogenesis to restore vascular loss after TBI through the Wnt/β-catenin signaling pathway. |
Abbreviations : TBI, FGF20, TJ, BBB, bFGF, PD, rhFGF20, VEGFA, IGF-1, CCI, CNS, IP, EB, PBS, WW, DW, BSA, HE, BrdU, mNSS, MWM, EBM-2
Keywords : RhFGF20, Traumatic brain injury, Angiogenesis, Blood-brain barrier, Wnt/β-catenin
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Vol 143
Article 112200- novembre 2021 Retour au numéro
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