Abstract

Congenital heart disease (CHD) is a type of major defect that occurs during embryonic development. Although significant advances have been made in the treatment of CHD, its etiology and molecular mechanism remain unclear. To identify the critical role of SUMOylation in cardiac development, we generated SENP3 knockout mice and showed that SENP3 knockout mice die on embryonic day 8.5 with an open neural tube and reversed left-right cardiac asymmetry. Moreover, SENP3 knockout promoted apoptosis and senescence of H9C2 cells. Further studies showed that Nodal, a critical gene that forms left-right asymmetry, is regulated by SENP3 and that SENP3 regulates cell apoptosis and senescence in a Nodal-dependent manner. Furthermore, Nodal was hyper-SUMOylated after SENP3 knockout, and SUMOylation of Nodal inhibited its ubiquitination and ubiquitin-proteasome degradation pathway. Nodal overexpression enhanced cell apoptosis and senescence; however, the mutation at the SUMOylation site of Nodal reversed its effect on the apoptosis and senescence of H9C2 cells. More importantly, the SENP3-Nodal axis regulates cell senescence by inducing cell autophagy. These results suggest that the SENP3-Nodal signaling axis regulates cardiac senescence-autophagy homeostasis, which in turn affects cardiac development and results in the occurrence of CHD.

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call

Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.