Repressing miR-23a promotes the transdifferentiation of pancreatic α cells to β cells via negatively regulating the expression of SDF-1α

Abstract

Abstract Pancreatic β-cell failure is a pathological feature in type 1 diabetes. One promising approach is the transdifferentiation of developmentally related pancreatic cell types, including glucagon-producing α cells. The chemokine stromal cell-derived factor-1 alpha (SDF-1α) is implicated in pancreatic α-to-β like cell transition. Here, the serum level of SDF-1α was lower in T1D with C-peptide loss, the miR-23a was negatively correlated with SDF-1α. We identify exosomal miR-23a secreted from β cells, functionally negatively regulate the expression of SDF-1α, followed by increased expression of Pax4 and decreased expression of Arx in vivo. Adenovirus-vectored miR-23a sponge and mimic were constructed to further explored the miR-23a on pancreatic α-to-β like cell transition in vitro, and the results were similar to cell experiments. Repression of miR-23a upregulated the level of insulin and downregulated the level of glucagon in αTCl-6 cells and STZ-induced diabetes mice models, promoting α-to-β like cell transition. Our results identified miR-23a as a new therapeutic target for the regeneration of pancreatic β cells from α cells.