NFAT and the regulation of Sca-1 in muscle cells

描述(由申请人提供)： 肌肉前体细胞(MPC)是肌肉生长和再生所必需的。SCA-1被认为可以负向调节MPC的生长和分化。初步数据表明，SCA-1受NFAT转录因子家族的调控。这项提案的目标是进一步调查和确定NFAT在SCA-1调控中的作用。特定的NFAT亚型在SCA-1激活中的作用将通过在肌肉中缺乏或过度表达NFAT蛋白的细胞(NFATc1-c3)来检验。为了确定NFAT是否直接激活SCA-1的表达，将研究NFAT与SCA-1启动子结合的能力；还将确定NFAT调控SCA-1启动子所必需和足够的区域。将研究参与肌肉生长和修复的生长因子对SCA-1表达的激活，并确定对NFAT的依赖。这些研究可能导致开发新的方法来处理疾病、再生和衰老中的肌源性干细胞，并确定促进肌肉生长的新的治疗靶点。

DESCRIPTION (provided by applicant): Muscle precursor cells (MPC) are essential for muscle growth and regeneration. Sca-1 has been proposed to negatively regulate growth and differentiation of MPC. Preliminary data suggest that Sca-1 is regulated by the NFAT family of transcription factors. The goal of this proposal is to further investigate and define the role of NFAT in Sca-1 regulation. The role of specific NFAT isoforms in Sca-1 activation will be examined using cells lacking or overexpressing NFAT proteins expressed in muscle (NFATc1-c3). To determine if NFAT directly activates Sca-1 expression, the ability of NFAT to bind the Sca-1 promoter will be investigated; the regions of the Sca-1 promoter necessary and sufficient for regulation by NFAT will also be determined. Activation of Sca-1 expression by growth factors involved in muscle growth and repair will be studied, and dependence on NFAT determined. These studies may result in the development of new methods for manipulating myogenic stem cells in disease, regeneration, and aging, as well as define new therapeutic targets for enhancing muscle growth.