Open AccessInhibition of SENP2-mediated Akt deSUMOylation promotes cardiac regeneration via activating Akt pathway
Author(s) -
Yijin Chen,
Tong Xu,
Mengsha Li,
Chuling Li,
Yue Ma,
Guojun Chen,
Yili Sun,
Hao Zheng,
Guangkai Wu,
Wangjun Liao,
Yulin Liao,
Yanmei Chen,
Jianping Bin
Publication year - 2021
Publication title -
clinical science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.91
H-Index - 138
eISSN - 1470-8736
pISSN - 0143-5221
DOI - 10.1042/cs20201408
Subject(s) - sumo protein , protein kinase b , angiogenesis , microbiology and biotechnology , biology , pi3k/akt/mtor pathway , regeneration (biology) , proteases , ubiquitin , signal transduction , cancer research , biochemistry , enzyme , gene
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 GSK3β 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.