Silenced CHOP protects pancreatic B-cell function by targeting peroxisome proliferator-activated receptor-γ...

Diabetes mellitus (DM) is one of the most common metabolic diseases worldwide characterized by insulin resistance and pancreatic β-cell dysfunction. In the previous study, endoplasmic reticulum (ER) stress could increase the C/EBP homologous protein (CHOP) expression through inhibiting C/EBβ transcriptional activity. However, the role of CHOP and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) in pancreatic β-cell dysfunction remains unknown. The aim of the study was to investigate the effect of CHOP and PGC-1α in pancreatic β-cell dysfunction and the potential mechanisms underlying its actions.

We established the pancreatic β-cell dysfunction model to identify the biological features and functions of CHOP. Apoptosis was detected using Western blot analysis and real-time polymerase chain reaction (RT-PCR).

Our results showed that high glucose (HG) increases CHOP and inhibits PGC-1α expression and ameliorates apoptosis in pancreatic β cells. Silenced CHOP elevates the PGC-1α expression and ameliorates HG-induced apoptosis in pancreatic β cells. Furthermore, upregulation of the PGC-1α alleviates HG-induced apoptosis in pancreatic β cells. We also expounded that HG-activated phosphorylation of nuclear factor-κB through increasing PGC-1α expression.

We verified the function and mechanism of CHOP and provide evidence that CHOP and PGC-1α may serve as potential candidates for the clinical treatment of DM.