MBNL2 promotes aging-related cardiac fibrosis via inhibited SUMOylation of Kruppel-like factor4.

ABSTRACT: Aging-related cardiac fibrosis represents the principal pathological progression in cardiovascular aging. The Muscleblind-like splicing regulator 2 (MBNL2) has been unequivocally established as being associated with cardiovascular diseases. Nevertheless, its role in aging-related cardiac fibrosis remains unexplored. This investigation revealed an elevation of MBNL2 levels in the aged heart and senescent cardiac fibroblasts. Notably, the inhibition of MBNL2 demonstrated a capacity to mitigate H₂O₂-induced myofibroblast transformation and aging-related cardiac fibrosis. Further mechanistic exploration unveiled that aging heightened the expression of SENP1 and impeded the SUMO1 binding with KLF4, and SUMOylation of KLF4 effectively increased by the inhibition of MBNL2. A

SUBMITTER: Lu J 

PROVIDER: S-EPMC11226984 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature