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Am J Physiol Cell Physiol (October 15, 2003). doi:10.1152/ajpcell.00211.2003
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Submitted on May 21, 2003
Accepted on October 9, 2003

Rapid Muscle-Specific Gene Expression Changes After A Single Bout of Eccentric Contractions in the Mouse

Ilona A Barash1, Liby Mathew1, Allen F Ryan2, Ju Chen3, and Richard L Lieber1*

1 Orthopaedics and Bioengineering, University of California, La Jolla, CA, USA
2 Surgery, University of California, La Jolla, CA, USA
3 Medicine, University of California, La Jolla, CA, USA

* To whom correspondence should be addressed. E-mail: rlieber{at}ucsd.edu.

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 eccentric contraction-induced injury has been studied in detail, muscle's biological response 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 hours after ECs to both isometrically stimulated muscles and contralateral muscles. Torque dropped by about 55% immediately after the exercise bout, and recovered to initial levels 7 days later. 36 known genes were upregulated after ECs compared to contralateral and isometrically stimulated muscles, including five muscle specific genes: muscle LIM protein (MLP), Muscle Ankyrin Repeat Proteins (MARP 1 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 hours after the EC bout and returning to baseline within 72 hours. 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.




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