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Am J Physiol Cell Physiol 286: C355-C364, 2004. First published October 15, 2003; doi:10.1152/ajpcell.00211.2003
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MUSCLE CELL BIOLOGY AND CELL MOTILITY

Rapid muscle-specific gene expression changes after a single bout of eccentric contractions in the mouse

Ilona A. Barash, Liby Mathew, Allen F. Ryan, Ju Chen, and Richard L. Lieber

Departments of Orthopaedics, Bioengineering, Surgery, and Medicine and the Biomedical Sciences Graduate Group, University of California and Department of Veterans Affairs Medical Centers, San Diego, California 92161

Submitted 21 May 2003 ; accepted in final form 9 October 2003

Eccentric contractions (ECs), in which a muscle is forced to lengthen while activated, result in muscle injury and, eventually, muscle strengthening and prevention of further injury. Although the mechanical basis of EC-induced injury has been studied in detail, the biological response of muscle is less well characterized. This study presents the development of a minimally invasive model of EC injury in the mouse, follows the time course of torque recovery after an injurious bout of ECs, and uses Affymetrix microarrays to compare the gene expression profile 48 h after ECs to both isometrically stimulated muscles and contralateral muscles. Torque dropped by ~55% immediately after the exercise bout and recovered to initial levels 7 days later. Thirty-six known genes were upregulated after ECs compared with contralateral and isometrically stimulated muscles, including five muscle-specific genes: muscle LIM protein (MLP), muscle ankyrin repeat proteins (MARP1 and -2; also known as cardiac ankyrin repeat protein and Arpp/Ankrd2, respectively), Xin, and myosin binding protein H. The time courses of MLP and MARP expression after the injury bout (determined by quantitative real-time polymerase chain reaction) indicate that these genes are rapidly induced, reaching a peak expression level of 6–11 times contralateral values 12–24 h after the EC bout and returning to baseline within 72 h. Very little gene induction was seen after either isometric activation or passive stretch, indicating that the MLP and MARP genes may play an important and specific role in the biological response of muscle to EC-induced injury.

muscle LIM protein; cardiac ankyrin repeat protein; muscle ankyrin repeat protein; microarray


Address for reprint requests and other correspondence: R. L. Lieber, Dept. of Orthopaedics (9151), VA Medical Center and Univ. of California-San Diego, 3350 La Jolla Village Dr., San Diego, CA 92161 (E-mail: rlieber{at}ucsd.edu).




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