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- Title
Inhibition of SENP2-mediated Akt deSUMOylation promotes cardiac regeneration via activating Akt pathway.
- Authors
Yijin Chen; Tong Xu; Mengsha Li; Chuling Li; Yusheng Ma; Guojun Chen; Yili Sun; Hao Zheng; Guangkai Wu; Wangjun Liao; Yulin Liao; Yanmei Chen; Jianping Bin
- Abstract
Post-translational modification (PTM) by small ubiquitin-like modifier (SUMO) is a key regulator of cell proliferation and can be readily reversed by a family of SUMO-specific proteases (SENPs), making SUMOylation an ideal regulatory mechanism for developing novel therapeutic strategies for promoting a cardiac regenerative response. However, the role of SUMOylation in cardiac regeneration remains unknown. In the present study, we assessed whether targeting protein kinase B (Akt) SUMOylation can promote cardiac regeneration. Quantitative PCR and Western blotting results showed that small ubiquitin-like modifier-specific protease 2 (SENP2) is up-regulated during postnatal heart development. SENP2 deficiency promoted P7 and adult cardiomyocyte (CM) dedifferentiation and proliferation both in vitro and in vivo. Mice with SENP2 deficiency exhibited improved cardiac function after MI due to CM proliferation and angiogenesis. Mechanistically, the loss of SENP2 up-regulated Akt SUMOylation levels and increased Akt kinase activity, leading to a decrease in GSK3ß levels and subsequently promoting CM proliferation and angiogenesis. In summary, inhibition of SENP2-mediated Akt deSUMOylation promotes CM differentiation and proliferation by activating the Akt pathway. Our results provide new insights into the role of SUMOylation in cardiac regeneration.
- Subjects
CARDIAC regeneration; PROTEIN kinase B; HEART development; POST-translational modification; WESTERN immunoblotting; GRANZYMES
- Publication
Clinical Science, 2021, Vol 135, Issue 6, p811
- ISSN
0143-5221
- Publication type
Article
- DOI
10.1042/CS20201408