JAK/STAT Pathway in Skeletal Muscle Pathophysiology
Abstract
The Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway is a key intracellular mediator of a variety of metabolically relevant hormones and cytokines, including the interleukin-6 (IL-6) family of cytokines. The JAK/STAT pathway transmits extracellular signals to the nucleus, leading to the transcription of genes involved in multiple biological activities. The JAK/STAT pathway has been reported to be required for the homeostasis of different tissues and organs. Indeed, when deregulated, it promotes the initiation and progression of pathological conditions, including cancer, obesity, diabetes, and other metabolic diseases. In skeletal muscle, activation of the JAK/STAT pathway by the IL-6 cytokines accounts for opposite effects: on the one hand, it promotes muscle hypertrophy, by increasing the proliferation of satellite cells; on the other hand, it contributes to muscle wasting. The expression of IL-6 and of key members of the JAK/STAT pathway is regulated at the epigenetic level through histone methylation and histone acetylation mechanisms. Thus, manipulation of the JAK/STAT signaling pathway by specific inhibitors and/or drugs that modulate epigenetics is a promising therapeutic intervention for the treatment of numerous diseases. We focus this review on the JAK/STAT pathway functions in striated muscle pathophysiology and the potential role of IL-6 as an effector of the cross talk between skeletal muscle and other organs.
Additional Information
© 2019 Moresi, Adamo and Berghella. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Received: 25 November 2018; Accepted: 08 April 2019; Published: 30 April 2019. Author Contributions: All authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication. VM and SA are supported by Sapienza University research grants. LB is supported by the French Muscular Dystrophy Association (AFM-Telethon). The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.Attached Files
Published - fphys-10-00500.pdf
Files
Name | Size | Download all |
---|---|---|
md5:54932af6cd3b39c6c5307e90810a27e0
|
1.5 MB | Preview Download |
Additional details
- Eprint ID
- 95518
- Resolver ID
- CaltechAUTHORS:20190515-142709001
- Sapienza University
- French Muscular Dystrophy Association
- Created
-
2019-05-15Created from EPrint's datestamp field
- Updated
-
2021-11-16Created from EPrint's last_modified field