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BioMed Research International - Volume 2015 2015, Article ID 843743, 7 pages -

Research Article

Research Center for Genetic Medicine, Children’s National Medical Center, 111 Michigan Avenue, NW, Washington, DC 20010, USA

Neuromuscular and Neurogenetic Disorders of Childhood Section, Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, 35 Convent Drive, Building 35, Room 2A116, Bethesda, MD 20892, USA

Department of Integrative Systems Biology and Department of Pediatrics, George Washington University, 2121 I Street Northwest, Washington, DC 20052, USA

Received 20 January 2015; Accepted 30 March 2015

Academic Editor: Toshifumi Yokota

Copyright © 2015 Eleonora Guadagnin et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Transforming growth factor beta 1 TGFβ1 is a key player in skeletal muscle degenerative and regenerative processes. We previously showed that conditionally overexpressing TGFβ1 in skeletal muscles caused myofiber atrophy and endomysial fibrosis in mice. However, the disease severity varied significantly among individual mice. While 40% of mice developed severe muscle pathology and lost body weight within 2 weeks of TGFβ1 transgene induction in muscles, the rest showed milder or no phenotype. This study aims at determining whether signal transducer and activator of transcription 3 STAT3 plays a role in the phenotypic difference and whether it can be activated by TGFβ1 directly in muscle cells. Our results show that while total STAT3 was not differentially expressed between the two groups of mice, there was significantly higher pSTAT3 Tyr705 in the muscles of the mice with severe phenotype. Immunohistochemistry showed that pSTAT3 Tyr705 was localized in approximately 50% of the nuclei of the muscles. We further showed that TGFβ1 induced Tyr705 phosphorylation of STAT3 in C2C12 cells within 30 minutes of treatment while total STAT3 was not affected. Our findings suggest that TGFβ1 alone can induce Tyr705 phosphorylation of STAT3 in skeletal muscle cells and contribute to disease severity in transgenic TGFβ1 mice.

Autor: Eleonora Guadagnin, Jigna Narola, Carsten G. Bönnemann, and Yi-Wen Chen

Fuente: https://www.hindawi.com/


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