Follistatin-like 1 protects cardiomyoblasts from injury induced by sodium nitroprusside through modulating Akt and Smad1/5/9 signaling.

Cardiac cell apoptosis provoked by excessive sodium nitroprusside (SNP) toxicity, a potent vasodilator, limited its clinical application. Effective means for protection against SNP-induced cardiotoxicity would be highly needed. This study investigated the effects of Follistatin-like 1 (FSTL1) on the injury induced by SNP in rat cardiomyoblast H9c2 cells. First, expression of FSTL is attenuated following SNP treatment. SNP challenge significantly increases cardiac cell death, which is attenuated by FSTL1 pretreatment. Additionally, knockdown of endogenous FSTL1 enhances SNP-induced cell apoptosis. Furthermore, FSTL1 pretreatment partially inhibits SNP-induced NO generation. LY294002 and BMP4 completely abolish cytoprotective role of FSTL1 against SNP challenge, indicating both activation of Akt and inhibition of BMP/Smad1/5/9 signaling are involved in this cellular process. Lastly, FSTL1-mediated cytoprotection is independent of Smad2/3 signaling, as SB525334 fails to remove its protective role. Taken together, these results indicated that FSTL1 protects the SNP-induced injury in cardiac H9c2 cells through, at least in part, the activation of Akt and inhibition of Smad1/5/9 signaling.