Diesel exhaust particles induce toxicity to beta cells by suppressing miR-140-5p.

ABSTRACT

The toxicologic effects of diesel exhaust particles (DEPs) on lung cells and function have been heavily studied. However, it remains largely unknown how DEPs affect the function of pancreatic beta cells. In this study, wedemonstrated that DEP extract (DPE) exposure significantly reduces cell viability, insulin secretion, and ATP and GSH production of rat pancreatic beta cells. Also, DPEs induce the accumulation of ROS, p53 expression, and DNA damage in beta cells. In addition, the expression level of miR-140-5p was downregulated in beta cells following DPE exposure, and ectopic expression of miR-140-5p could partly attenuate the toxic effects of DPEs. Mechanistically, HDCA4 and HDCA7 were downstream targets of miR-140-5p. In conclusion, our findingsdemonstrate that DPE exposure impairs the normal functions of beta cells by downregulating miR-140-5p. Further studies are warranted to explore the toxic effects of circulating DEPs on the pancreas.