Regulation of Autophagy and Ubiquitinated Protein Accumulation by BFGF Promotes Functional Recovery and Neural Protection in a Rat Model of Spinal Cord Injury

Overview

Journal Mol Neurobiol

Specialties Molecular Biology
Neurology

Date 2013 Mar 22

PMID 23516099

Citations 96

Authors

Hong-Yu Zhang

Zhou-Guang Wang

Fen-Zan Wu

Xiao-Xia Kong

Jie Yang

Bei-Bei Lin

Shi-Ping Zhu

Li Lin

Chao-Shi Gan

Xiao-Bing Fu

Xiao-Kun Li

Hua-Zi Xu

Jian Xiao

Affiliations

Soon will be listed here.

Abstract

The role of autophagy in the recovery of spinal cord injury remains controversial; in particular, the mechanism of autophagy regulated degradation of ubiquitinated proteins has not been discussed to date. In this study, we investigated the protective role of basic fibroblast growth factor (bFGF) both in vivo and in vitro and demonstrated that excessive autophagy and ubiquitinated protein accumulation is involved in the rat model of trauma. bFGF administration improved recovery and increased the survival of neurons in spinal cord lesions in the rat model. The protective effect of bFGF is related to the inhibition of autophagic protein LC3II levels; bFGF treatment also enhances clearance of ubiquitinated proteins by p62, which also increases the survival of neuronal PC-12 cells. The activation of the downstream signals of the PI3K/Akt/mTOR pathway by bFGF treatment was detected both in vivo and in vitro. Combination therapy including the autophagy activator rapamycin partially abolished the protective effect of bFGF. The present study illustrates that the role of bFGF in SCI recovery is related to the inhibition of excessive autophagy and enhancement of ubiquitinated protein clearance via the activation of PI3K/Akt/mTOR signaling. Overall, our study suggests a new trend for bFGF drug development for central nervous system injuries and sheds light on protein signaling involved in bFGF action.

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