FGF10 Enhances Peripheral Nerve Regeneration via the Preactivation of the PI3K/Akt Signaling-Mediated Antioxidant Response

Lvpeng Dong; Rui Li; Duohui Li; Beini Wang; Yingfeng Lu; Peifeng Li; Fangzheng Yu; Yonglong Jin; Xiao Ni; Yanqing Wu; Shengnan Yang; Guanxi Lv; Xiaokun Li; Jian Xiao; Jian Wang

doi:10.3389/fphar.2019.01224

FGF10 Enhances Peripheral Nerve Regeneration via the Preactivation of the PI3K/Akt Signaling-Mediated Antioxidant Response

Front Pharmacol. 2019 Oct 16:10:1224. doi: 10.3389/fphar.2019.01224. eCollection 2019.

Authors

Lvpeng Dong^{1

2}, Rui Li^{2

3}, Duohui Li², Beini Wang², Yingfeng Lu¹, Peifeng Li¹, Fangzheng Yu¹, Yonglong Jin¹, Xiao Ni¹, Yanqing Wu², Shengnan Yang², Guanxi Lv², Xiaokun Li², Jian Xiao², Jian Wang¹

Affiliations

¹ Department of Hand Surgery and Peripheral Neurosurgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
² Molecular Pharmacology Research Center, School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, China.
³ School of Chemistry, Sun Yat-sen University, Guangzhou, China.

Abstract

The process of axonal regeneration after peripheral nerve injury (PNI) is slow and mostly incomplete. Previous studies have investigated the neuroprotective effects of fibroblast growth factor 10 (FGF10) against spinal cord injury and cerebral ischemia brain injury. However, the role of FGF10 in peripheral nerve regeneration remains unknown. In this study, we aimed to investigate the underlying therapeutic effects of FGF10 on nerve regeneration and functional recovery after PNI and to explore the associated mechanism. Our results showed that FGF10 administration promoted axonal regeneration and functional recovery after nerve damage. Moreover, exogenous FGF10 treatment also prevented SCs from excessive oxidative stress-induced apoptosis, which was probably related to the activation of phosphatidylinositol-3 kinase/protein kinase B (PI3K/Akt) signaling. The inhibition of the PI3K/Akt pathway by the specific inhibitor LY294002 partially reversed the therapeutic effects of FGF10 both in vivo and in vitro. Thus, from our perspective, FGF10 may be a promising therapeutic drug for repairing sciatic nerve damage through countering excessive oxidative stress-induced SC apoptosis.

Keywords: apoptosis; axonal regeneration; fibroblast growth factor 10; oxidative stress; peripheral nerve injury.