Transcriptional pathways associated with skeletal muscle disuse atrophy in humans

@article{citeulike:2433487, abstract = {Disuse atrophy is a common clinical phenomenon that significantly impacts muscle function and activities of daily living. The purpose of this study was to implement genome-wide expression profiling to identify transcriptional pathways associated with muscle remodeling in a clinical model of disuse. Skeletal muscle biopsies were acquired from the medial gastrocnemius in patients with an ankle fracture and from healthy volunteers subjected to 411 days of cast immobilization. We identified 277 misregulated transcripts in immobilized muscles of patients, of which the majority were downregulated. The most broadly affected pathways were involved in energy metabolism, mitochondrial function, and cell cycle regulation. We also found decreased expression in genes encoding proteolytic proteins, calpain-3 and calpastatin, and members of the myostatin and IGF-I pathway. Only 26 genes showed increased expression in immobilized muscles, including apolipoprotein (APOD) and leptin receptor (LEPR). Upregulation of APOD (5.0-fold, P < 0.001) and LEPR (5.7-fold, P < 0.05) was confirmed by quantitative RT-PCR and immunohistochemistry. In addition, atrogin-1/MAFbx was found to be 2.4-fold upregulated (P < 0.005) by quantitative RT-PCR. Interestingly, 96\% of the transcripts differentially regulated in immobilized limbs also showed the same trend of change in the contralateral legs of patients but not the contralateral legs of healthy volunteers. Information obtained in this study complements findings in animal models of disuse and provides important feedback for future clinical studies targeting the restoration of muscle function following limb disuse in humans. 10.1152/physiolgenomics.00115.2006}, author = {Chen, Yi-Wen and Gregory, Chris M. and Scarborough, Mark T. and Shi, Rongye and Walter, Glenn A. and Vandenborne, Krista }, citeulike-article-id = {2433487}, doi = {10.1152/physiolgenomics.00115.2006}, journal = {Physiol. Genomics}, month = {November}, number = {3}, pages = {510--520}, posted-at = {2008-02-27 05:23:06}, priority = {2}, title = {Transcriptional pathways associated with skeletal muscle disuse atrophy in humans}, url = {http://dx.doi.org/10.1152/physiolgenomics.00115.2006}, volume = {31}, year = {2007} }

TY - JOUR ID - citeulike:2433487 L3 - citeulike-article-id:2433487 TI - Transcriptional pathways associated with skeletal muscle disuse atrophy in humans JF - Physiol. Genomics VL - 31 IS - 3 SP - 510 EP - 520 N2 - Disuse atrophy is a common clinical phenomenon that significantly impacts muscle function and activities of daily living. The purpose of this study was to implement genome-wide expression profiling to identify transcriptional pathways associated with muscle remodeling in a clinical model of disuse. Skeletal muscle biopsies were acquired from the medial gastrocnemius in patients with an ankle fracture and from healthy volunteers subjected to 411 days of cast immobilization. We identified 277 misregulated transcripts in immobilized muscles of patients, of which the majority were downregulated. The most broadly affected pathways were involved in energy metabolism, mitochondrial function, and cell cycle regulation. We also found decreased expression in genes encoding proteolytic proteins, calpain-3 and calpastatin, and members of the myostatin and IGF-I pathway. Only 26 genes showed increased expression in immobilized muscles, including apolipoprotein (APOD) and leptin receptor (LEPR). Upregulation of APOD (5.0-fold, P < 0.001) and LEPR (5.7-fold, P < 0.05) was confirmed by quantitative RT-PCR and immunohistochemistry. In addition, atrogin-1/MAFbx was found to be 2.4-fold upregulated (P < 0.005) by quantitative RT-PCR. Interestingly, 96% of the transcripts differentially regulated in immobilized limbs also showed the same trend of change in the contralateral legs of patients but not the contralateral legs of healthy volunteers. Information obtained in this study complements findings in animal models of disuse and provides important feedback for future clinical studies targeting the restoration of muscle function following limb disuse in humans. 10.1152/physiolgenomics.00115.2006 AU - Chen, Yi-Wen AU - Gregory, Chris AU - Scarborough, Mark AU - Shi, Rongye AU - Walter, Glenn AU - Vandenborne, Krista PY - 2007/11/14/ UR - http://dx.doi.org/10.1152/physiolgenomics.00115.2006 ER -