Bromoindirubin-3′-oxime intercepts GSK3 signaling to promote and enhance skeletal muscle differentiation affecting miR-206 expression in mice

By Ragozzino, Elvira; Brancaccio, Mariarita; Di Costanzo, Antonella; Scalabri, Francesco; Andolfi, Gennaro; Wanderlingh, Luca G.; Patriarca, Eduardo J.; Minchiotti, Gabriella; Altamura, Sergio; Varrone, Francesca; et al
From Scientific Reports (2019), 9(1), 18091. Language: English, Database: CAPLUS, DOI:10.1038/s41598-019-54574-4

To identify new and alternative compds. with a functional role in skeletal muscle myogenesis, we screened a library of pharmacol. active compds. and selected the small mol. 6-bromoindirubin-3′-oxime as an inhibitor of myoblast proliferation. Using C2C12 cells, we examd. BIO’s effect during myoblast proliferation and differentiation showing that BIO treatment promotes transition from proliferation to myogenic differentiation through the arrest of cell cycle. Here, we show that BIO able promote myogenic differentiation in damaged myotubes in-vitro by enriching population of newly formed skeletal muscle myotubes. Moreover, in-vivo expts. in CTX-damaged TA muscle confirmed the pro-differentiation capability of BIO as shown by the increasing of the percentage of myofibers with centralized nuclei as well as by the increasing of myofibers no. Addnl., we have identified a strong correlation of miR-206 with BIO treatment both in-vitro and in-vivo: the enhanced expression of miR-206 was obsd. in-vitro in BIO-treated proliferating myoblasts, miR-206 restored expression was obsd. in a forced miR-206 silencing conditions antagomiR-mediated upon BIO treatment, and in-vivo in CTX-injured muscles miR-206 enhanced expression was obsd. upon BIO treatment. Taken together, our results highlight the capacity of BIO to act as a pos. modulator of skeletal muscle differentiation in-vitro and in-vivo opening up a new perspective for novel therapeutic targets to correct skeletal muscle defects.