Dario Coletti

TNFα inhibits skeletal myogenesis through a PW1‐dependent pathway by recruitment of caspase pathways

Cachexia is associated with poor prognosis in patients with chronic disease. Tumor necrosis factor‐alpha (TNFα) plays a pivotal role in mediating cachexia and has been demonstrated to inhibit skeletal muscle differentiation in vitro. It has been proposed that TNFα‐mediated activation of NFκB leads to down regulation of MyoD, however the mechanisms underlying TNFα effects on skeletal muscle remain poorly understood. We report here a novel pathway by which TNFα inhibits muscle differentiation through activation of caspases in the absence of apoptosis. TNFα‐mediated caspase activation and block of differentiation are dependent upon the expression of PW1, but occur independently of NFκB activation. PW1 has been implicated previously in p53‐mediated cell death and can induce bax translocation to the mitochondria. We show that bax‐deficient myoblasts do not activate caspases and differentiate in the presence of TNFα, highlighting a role for bax‐dependent caspase activation in mediating TNFα effects. Taken together, our data reveal that TNFα inhibits myogenesis by recruiting components of apoptotic pathways through PW1.

Ormoni neuroipofisari: regolatori non canonici della struttura, funzione e omeostasi del muscolo

SommarioNuovi, inaspettati ruoli degli ormoni neuroipofisari vasopressina e ossitocina sono emersi negli ultimi decenni. Gli effetti di tali ormoni sul muscolo striato sono stati oggetto di numerose ricerche in vitro e in vivo che hanno generato un’importante serie di dati circa la segnalazione intracellulare in cellule miogeniche, la loro risposta differenziativa, lo sviluppo e l’omeostasi del muscolo scheletrico. Riassumiamo qui gli studi su questi nuovi ruoli degli ormoni neuroipofisari, che aprono anche la possibilità di nuovi approcci terapeutici a patologie muscolari.