Introduction The transcription factor ETV5 regulates various biological processes such as cell
proliferation and apoptosis, and activates a whole string of obesity- and diabetes-related
genes. ETV5 is involved in tissue protection since mice with pancreatic loss of Etv5
show increased severity of pancreatitis and delayed tissue recovery. Here, we investigate
the role of Etv5 knockdown (KD) on survival of injured endocrine pancreatic beta cells.
Methods We generated INS-1E beta cells with doxycycline-inducible lentiviral Etv5 sh-RNA
knock-down (KD). Cellular stress was induced by streptozotocin (STZ) and palmitate
(PA). We assessed viability (MTS), apoptosis (caspases-3/7 activation), necrosis (assay),
ER stress (BiP and CHOP gene expression), oxidative stress (ROS production) and gene
expression of SOD1, SOD2 and Catalase.
Results Etv5 KD significantly increases STZ / PA-induced loss of viability without changes
in apoptosis but with increased necrosis. Etv5 KD did not change STZ / PA-induced
gene expression of ER stress markers BiP and CHOP but significantly increased H2O2
production. STZ / PA induced SOD2 but not SOD1 and catalase. SOD2, which converts
superoxide into H2O2, was significantly further increased by Etv5 KD. In contrast,
catalase that degrades H2O2 into H2O and O2, was not affected.
Summary / Conclusion Obesity and high glucose promote oxidative stress and loss of Etv5 increases production
of both ROS and SOD2. Therefore, ETV5 may play an important role in the control of
oxidative stress in pancreatic β-cells.
Xuanzi Yi is supported by China Scolarship Council (CSC) China
