Differential calcineurin/NFATc1‐c3 signaling in the regulation of the skeletal muscle fiber phenotype

Abstract

Involvement of Cn/NFAT signaling in the regulation of the skeletal muscle fiber phenotype is recognized, however, the role of the various Cn‐regulated NFAT isoforms in this process remains rudimentary. We thus assessed the expression, localization and function of NFAT isoforms in muscle fibers of wild type or transgenic NFATc2 or NFATc3 deficient mice under normal weightbearing or functional compensatory work overload conditions. Immunohistochemical analyses indicated that NFAT isoforms have distinct roles in the regulation of muscle remodeling associated with compensatory growth. Semi‐quantitative RT‐PCR did not reveal compensatory up‐regulation of surviving NFAT isoform mRNA levels in transgenic mice. On the other hand, western blotting and immunofluorescence data showed NFAT protein localization to be differentially regulated during compensatory growth. Moreover, gene array analyses showed distinct gene expression patterns across conditions. Taken together, these results show that members of the NFAT family of transcription factors have distinct roles in the expression of the muscle fiber phenotype and a limited capacity to substitute for one another during conditions of rapid fiber growth. Supported by NSERC, CIHR and CRC to RNM. EMK is a CIHR scholar.