DENERVATION AND REINNERVATION OF ADULT SKELETAL MUSCLE MODULATE mRNA EXPRESSION OF NEUREGULIN-1 AND ERBB RECEPTORS

被引:19
作者
Nicolino, Silvia [1 ]
Panetto, Arianna [1 ]
Raimondo, Stefania [2 ]
Gambarotta, Giovanna [1 ]
Guzzini, Matteo [3 ]
Fornaro, Michele [2 ]
Battiston, Bruno [4 ]
Tos, Perluigi [4 ]
Geuna, Stefano [2 ]
Perroteau, Isabelle [1 ]
机构
[1] Univ Turin, Dipartimento Biol Anim & Uomo, I-10043 Turin, Italy
[2] Univ Turin, Osped San Luigi Gonzaga, Dipartimento Sci Clin & Biol, I-10043 Turin, Italy
[3] Univ Roma La Sapienza, Dipartimento Ortopedia & Traumatol, Osped S Andrea, Rome, Italy
[4] Osped CTO, Unita Operat Microchirurg Ricostrutt, Turin, Italy
关键词
PERIPHERAL-NERVE REGENERATION; VEIN-COMBINED GUIDES; RAT MEDIAN NERVE; MYOGENIC DIFFERENTIATION; NEUROMUSCULAR SYNAPSE; OLFACTORY-BULB; SCHWANN-CELLS; REPAIR; MOUSE; SYSTEM;
D O I
10.1002/micr.20636
中图分类号
R61 [外科手术学];
学科分类号
摘要
Skeletal muscle atrophy represents one of the main causes of poor outcome of microsurgical nerve reconstruction. Recent studies have pointed to the importance of the neuregulin/ErbB signaling pathway in the development and regeneration of the neuromuscular system. Here, we show by immunohistochemistry, RT-PCR, and Western blotting analyses, in an in vivo model of adult skeletal muscle denervation/reinnervation, that expression of Neuregulin1 (NRG1) and ErbB receptors is regulated by the innervation condition. We found out that a significant upregulation of the alpha-, but not beta-, isoform of NRG1, as well as of ErbB2, ErbB3, and ErbB4-cyt1 isoform occurs as a consequence of denervation of flexor digitorum muscles of the rat forelimb by median nerve transection. Moreover, after tubulization median nerve repair, and consequent muscle reinnervation, all messengers of the NRG1/ErbB system are promptly downregulated. Therefore, our results suggest the existence of a alpha-NRG1-mediated autocrine and/or paracrine trophic loop in skeletal muscles that is activated after denervation and promptly deactivated after nerve reconstruction. This myotrophic loop is a promising therapeutic target for the prevention of muscle atrophy. Yet, the recent demonstration of a similar alpha-NRG1-mediated gliotrophic loop in denervated Schwann cells provides a possible explanation for the effectiveness of muscle conduits for tubulization nerve repair. (C) 2009 Wiley-Liss, Inc. Microsurgery 29:464-472, 2009.
引用
收藏
页码:464 / 472
页数:9
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