Secretion of EGF-like domain of heregulinβ promotes axonal growth and functional recovery of injured sciatic nerve

被引：31

作者：

Joung, Insil ^{[3
]}

Yoo, Minjoo ^{[1
,2
]}

Woo, Ji Hyoun ^{[1
,2
]}

Chang, Chi Young ^{[1
,2
]}

Heo, Hwon ^{[1
,2
]}

Kwon, Yunhee Kim ^{[1
,2
]}

机构：

[1] Kyung Hee Univ, Dept Biol, Seoul 130701, South Korea

[2] Kyung Hee Univ, Dept Life & Nanopharmaceut Sci, Seoul 130701, South Korea

[3] Hanseo Univ, Dept Biol Sci, Seosan 352820, South Korea

来源：

MOLECULES AND CELLS | 2010年 / 30卷 / 05期

关键词：

adenovirus; axonal growth; HRG beta; regeneration; sciatic nerve; sensory and motor function; PERIPHERAL-NERVE; GENE-TRANSFER; NEUREGULIN; CELL; EXPRESSION; REGENERATION; MODEL; RECEPTORS; VECTORS; GAP-43;

D O I：

10.1007/s10059-010-0137-5

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Neuregulin 1 (NRG1) and epidermal growth factor receptor (ErbB) signaling pathways control Schwann cells during axonal regeneration in an injured peripheral nervous system. We investigated whether a persistent supply of recombinant NRG1 to the injury site could improve axonal growth and recovery of sensory and motor functions in rats during nerve regeneration. We generated a recombinant adenovirus expressing a secreted form of EGF-like domain from Heregulin beta (sHRG beta E-Ad). This virus, sHRG beta E-Ad allowed for the secretion of 30-50 ng of small sHRG beta E peptides per 10(7-8) virus particle outside cells and was able to phosphorylate ErbB receptors. Transduction of the concentrated sHRG beta E-Ad into an axotomy model of sciatic nerve damage caused an effective promotion of nerve regeneration, as shown by histological features of the axons and Schwann cells, as well as increased expression of neurofilaments, GAP43 and S100 in the distal stump of the injury site. This result is consistent with longer axon lengths and thicker calibers observed in the sHRG beta E-Ad treated animals. Furthermore, sensory and motor functions were significantly improved in sHRG beta E-Ad treated animals when evaluated by a behavioral test. These results suggest a therapeutic potential for sHRG beta E-Ad in treatment of peripheral nerve injury.

引用

页码：477 / 484

页数：8

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