%0 Journal Article
%T Role of TGF-¦Â signaling in inherited and acquired myopathies
%A Tyesha N Burks
%A Ronald D Cohn
%J Skeletal Muscle
%D 2011
%I BioMed Central
%R 10.1186/2044-5040-1-19
%X The transforming growth factor-beta (TGF-¦Â) superfamily plays a crucial role in normal physiology and pathogenesis in a number of tissues. It is important to emphasize that downstream effects of this signaling cascade are often tissue-specific, thereby dictating which target genes will be activated in response to the transduction signal. Given its multifaceted effects in different tissues, deregulation of TGF-¦Â signaling cascades can lead to a multitude of developmental defects and/or disease [1]. Several members of the TGF-¦Â family have been shown to play important roles in regulating muscle growth and atrophy. The most extensively characterized ligands, in terms of the effects on skeletal muscle, are TGF-¦Â1, mitogen-activated protein kinases (MAPKs), and myostatin. In this review, we focus on these signaling molecules in normal homeostasis and pathological conditions affecting skeletal muscle and describe the therapeutic avenues that have recently been explored to target the TGF-¦Â signaling cascade.The TGF-¦Â superfamily of cytokines consists of a variety of signaling molecules including isoforms of TGF-¦Â (1 to 3), bone morphogenic proteins (BMPs 1 to 20), growth and differentiation factors (GDFs), activins (A and B), inhibins (A and B), nodal, leftys (1 and 2), and Mullerian inhibiting substance [1]. They are generally divided into two branches defined by the utilization of receptor Smads (R-Smads): the TGF-¦Â branch, consisting of TGF-¦Â, activin, Nodal, and myostatin (GDF-8), signals through R-Smads 2 and 3 and the BMP branch, consisting of BMPs and other GDFs, signals through R-Smads 1, 5 and 8. This superfamily is known to be involved in embryonic development, adult tissue homeostasis, and disease pathogenesis. Specifically, it has been shown to control proliferation, differentiation, apoptosis, migration, extracellular matrix (ECM) remodeling, immune functions, and tumor invasion/metastasis [2].TGF-¦Â1 is synthesized as a precursor that is cleaved intracellularl
%U http://www.skeletalmusclejournal.com/content/1/1/19