International Journal of Physical Medicine & Rehabilitation
Open Access

Abstract

Rapid Changes in NFAT-directed Transcriptional Activity after Muscle Paralysis Induced by a Spinal Cord Injury

Yasinee Rotratsirikun and Robert J. Talmadge

In skeletal muscles, the calcineurin - nuclear factor of activated T-cells (NFAT) pathway has been implicated as a positive regulator of the slow muscle phenotype. Spinal cord transection (ST) results in muscle paralysis and a slow to fast shift in muscle phenotype in the normally slow soleus muscle of rats. Therefore, to determine if the NFAT pathway could mediate the slow to fast shift after ST, NFAT-directed transcription was assessed in the soleus muscle of rats after ST. Seven days after ST, a significant down-regulation in the activity of an exogenous NFAT sensor promoter-reporter construct was observed (~20% of control levels). Second, RT-PCR analyses revealed that MCIP1.4 mRNA, an endogenous indicator of NFAT-directed transcriptional activation, was decreased by ~80% relative to controls when normalized to β-actin mRNA levels. Similarly, real time RT-PCR showed a down-regulation in the relative levels of MCIP1.4 mRNA at 1 day (92% reduction) and 7 days (89% reduction) after ST relative to control levels. These data demonstrate that NFAT-directed transcriptional activity is rapidly down-regulated following a reduction in neuromuscular activity. Since ST also results in a slow to fast shift in phenotypic protein expression, the down-regulation of NFAT transcriptional activity is consistent with a role for the calcineurin - NFAT pathway in down regulating slow muscle phenotypic gene expression after ST.