Fibroblast Growth Factor 13 Facilitates Peripheral Nerve Regeneration through Maintaining Microtubule Stability

Rui Li,Yanqing Wu,Xuetao Tao,Yan Peng,Jiahong Liang,Minghong Huang,Yongsheng Jiang,Ji Bihl

doi:10.1155/2021/5481228

Abstract

Peripheral nerve injury (PNI), resulting in the impairment of myelin sheaths and axons, seriously affects the transmission of sensory or motor nerves. Growth factors (GFs) provide a biological microenvironment for supporting nerve regrowth and have become a promising alternative for repairing PNI. As one number of intracellular growth factor family, fibroblast growth factor 13 (FGF13) was regard as a microtubule-stabilizing protein for regulating cytoskeletal plasticity and neuronal polarization. However, the therapeutic efficiency and underlying mechanism of FGF13 for treating PNI remained unknown. Here, the application of lentivirus that overexpressed FGF13 was delivered directly to the lesion site of transverse sciatic nerve for promoting peripheral nerve regeneration. Through behavioral analysis and histological and ultrastructure examinations, we found that FGF13 not only facilitated motor and sense functional recovery but also enhanced axon elongation and remyelination. Furthermore, pretreatment with FGF13 also promoted Schwann cell (SC) viability and upregulated the expression cellular microtubule-associated proteins in vitro PNI model. These data indicated FGF13 therapeutic effect was closely related to maintain cellular microtubule stability. Thus, this work provides the evident that FGF13-medicated microtubule stability is necessary for promoting peripheral nerve repair following PNI, highlighting the potential therapeutic value of FGF13 on ameliorating injured nerve recovery.

Highlights

Peripheral nerve injury (PNI) is one of the most traumatic disorders for triggering a decrease or a complete loss of motor and sensory function in clinical practice [1]
We aim to identify whether fibroblast growth factor 13 (FGF13) has a certain capability for improving the injured peripheral nerve regeneration in a rat model and reveal its underlying molecular mechanism via various comprehensive evaluations, including histological, morphological, and functional assessments
Our results provide evidence that, following PNI, overexpressing FGF13 substantively ameliorated sensory and motor functional recovery and remarkably promoted the morphological and pathological alterations, including axonal regrowth, myelin rehabilitation, and fibrotic scar reduction, as well as apoptotic decrease

Summary

Introduction

Peripheral nerve injury (PNI) is one of the most traumatic disorders for triggering a decrease or a complete loss of motor and sensory function in clinical practice [1]. Recent advances in nerve reconstruction and autologous nerve grafting remain the gold standard technique for the repair of acute nerve injury; these treatments exist some limitations, including the limited amount of autologous donor nerves, neuronal mismatch between the donor and the recipient site, even neuroma formation at the donor site [5, 6] To overcome these limitations, current therapeutic strategies are focused on administration of exogenous growth. Several preclinical trials have described that exogenous application of GFs to the lesion site of peripheral nerve is able to stimulate axonal sprouting, myelination, neurogenesis, and/or neovascularization [8,9,10] These encouraging outcomes reveal that GFs may act as the potent therapeutic drugs for repairing PNI. Based on the above fact, we try to reveal whether FGF13 plays an essential role on restoring PNI recovery

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