Silencing of the small GTPase DIRAS3 induces cellular senescence in human white adipose stromal/progenitor cells.

ABSTRACT: Inhibition of Akt-mTOR signaling protects from obesity and extends life span in animals. In the present study, we analyse the impact of the small GTPase, GTP-binding RAS-like 3 (DIRAS3), a recently identified weight-loss target gene, on cellular senescence in adipose stromal/progenitor cells (ASCs) derived from human subcutaneous white adipose tissue (sWAT). We demonstrate that DIRAS3 knock-down (KD) in ASCs induces activation of Akt-mTOR signaling and proliferation arrest. DIRAS3 KD ASCs lose the potential to form colonies and are negative for Ki-67. Moreover, silencing of DIRAS3 results in a premature senescence phenotype. This is characterized by senescence-associated β-galactosidase positive enlarged ASCs containing increased p16^INK4A level and activated retinoblastom

SUBMITTER: Ejaz A 

PROVIDER: S-EPMC5391236 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature