The Anti-apoptotic Role of 3'-Untranslational Region in Response to Angiotensin II via Mcl1 Expression

Dayin Lyu; Hong Yan; Liyang Chen; Lingmin Zhang; Yanfeng Du; Lexi Ding; Qiulun Lu

doi:10.3389/fcell.2020.593955

The Anti-apoptotic Role of 3'-Untranslational Region in Response to Angiotensin II via Mcl1 Expression

Front Cell Dev Biol. 2021 Jan 5:8:593955. doi: 10.3389/fcell.2020.593955. eCollection 2020.

Authors

Dayin Lyu¹, Hong Yan², Liyang Chen¹, Lingmin Zhang¹, Yanfeng Du¹, Lexi Ding³, Qiulun Lu¹

Affiliations

¹ Key Laboratory of Cardiovascular and Cerebrovascular Medicine, School of Pharmacy, Nanjing Medical University, Nanjing, China.
² Laboratory Medicine Center, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China.
³ Eye Center of Xiangya Hospital, Hunan Key Laboratory of Ophthalmology, Central South University, Changsha, China.

Abstract

Myeloid cell leukemia 1 (Mcl1), an abundant protein in the myocardium, plays an essential role in fibrosis and anti-inflammation in cardiomyocytes to prevent heart failure. However, whether Mcl1 3'-untranslated regions (3'-UTR) has the cardio-protecting function remains unclear. Down-regulation of Mcl1 was observed in adult mice heart tissues after Angiotensin II (Ang II) treatment. Consistent with in vivo results, the reduction of Mcl1 expression was identified in Ang II-treated neonatal cardiomyocytes. Mechanistically, Mcl1 3'-UTR prevented Ang II-induced cardiac apoptosis via up-regulation of Mcl1 and an angiogenic factor with a G-patch domain and a forkhead-associated domain 1 (Aggf1), which plays cardiac-protective role. Our work broadens the scope of gene therapy targets and provides a new insight into gene therapy strategies involving mRNAs' 3'-UTRs application.

Keywords: 3′-UTR; Ang II; Mcl1; anti-apoptosis; heart failure.