References:
- Li Y-P, Chen Y., John J., Moylan J., Jin B, Mann D.L. and Reid MB. TNF-a acts via p38 MAPK to stimulate expression of the ubiquitin ligase atrogin1/MAFbx in skeletal muscle. FASEB J. 19: 362-70, 2005.
- Chen S, Gerken E, Zhang Y, Mohan RK, Li AS, Reid MB, and Li Y-P. Role of TNF-a signaling in regeneration of cardiatoxin-injured muscle.Am. J. Physiol. – Cell Physiol. 289(5):C1179-87, 2005.
- Zhan M, Jin B, Chen S, Reecy JM, Li Y-P. TACE Release of TNF-α Mediates Mechanotransduction-Induced Activation of p38 MAPK and Myogenesis. J. Cell Sci. 15;120(Pt 4):692-701, 2007
- Jin B and Li Y-P. Curcumin Prevents Lipopolysaccharide-induced Atrogin-1/MAFbx Upregulation and Muscle Mass Loss. J. Cell. Biochem. 100:960-969, 2007.
- Chen S, Jin B, and Li Y-P. TNF-a Regulates myogenesis and muscle regeneration by activating p38 MAPK. Am. J. Physiol. – Cell Physiol. 292: C1660–C1671, 2007.
- Van Hees HWH, Li Y-P, Ottenheijm CAC, Jin B, Pigmans CJC, Linkels M, Dekhuijzen PNR and Heunks LMA. Proteasome inhibition improves diaphragm function in congestive heart failure rats. Am J Physiol Lung Cell Mol Physiol 294:1260-1268, 2008.
Yi-Ping Li, Ph.D.
Associate Professor
UTHSC, Medical School, (713) 500 - 6498
Yi-Ping.Li@uth.tmc.edu
Signaling Mechanism of Striated Muscle Remodeling
Striate muscle (skeletal and cardiac muscle) undergoes remodeling, either positive or negative, in response to physiological and pathological stress. For example, many inflammatory diseases including cancer, AIDS, sepsis, diabetes, and congestive heart failure induce debilitating muscle atrophy or wasting due to loss of muscle mass (cachexia). On the other hand, diseased or injured muscle has the capacity to regenerate leading to recovery of muscle mass and function. In addition, cardiac muscle chronically exposed to high blood pressure develops hypertrophy and eventually left ventricle dilation (congestive heart failure). The research in my lab is aimed to dissect the signaling mechanisms that regulate the remodeling processes using cellular and molecular approaches, and to test therapeutic strategies using in vitro and in vivo models. We are currently working on three research projects.
1. Mechanism of skeletal muscle wasting
Our lab and others have shown that inflammatory mediators that activate NF-κB and p38 MAPK play an important role in mediating muscle protein loss associated with many diseases. We investigate the signaling mechanisms of inflammatory mediator stimulation of the ubiquitin-proteasome pathway and the autophagy-lysosome pathway which are responsible for accelerated muscle protein degradation. We also conduct experimental therapy using animal models of muscle wasting and try to translate the basic research into clinical interventions for human patients.
2. Regulation of skeletal muscle regeneration
Skeletal muscle adapts to various stresses (injury, disease and training) by regenerating to make new muscle (myogenesis). Muscle regeneration is the function of muscle stem cells (also known as satellite cells) that have the capacity to proliferate, differentiate and fuse to form new muscle fibers when stimulated by myogenic cues. We study how these cells sense chemical or mechanical cues of myogenesis via their plasma membrane and activate specific intracellular signaling pathways that initiate muscle specific gene expression. We are particularly interested in the role of some membrane proteins including TNF-α converting enzyme (TACE) and integrins in regulating muscle gene expression.
3. Signaling mechanism of cardiac muscle adaptation to mechanical stress.
Cardiac muscle responds to chronic hemodynamic overloading (mechanical stress) by developing hypertrophy (adaptation) that leads to left ventricle dilation (maladaptation). We study the mechanotransduction mechanism that mediates cardiac muscle response to overloading with the purpose of identifying ways to prevent the maladaptation specifically without blocking adaptation. Particularly, we focus on the mechanism that mediates TACE activation by overloading.
