Abstract
Objective
Asprosin, a recently found adipokine, contributes to β cell dysfunction. Pyroptosis is a novel programmed cell death form. N6-Methyladenosine (m6A) modification has been implicated in many pathological processes. The purpose of this research is to ascertain whether asprosin affects the pyroptosis of β cell, as well as the possible role of m6A modification in this process.
Method
Then the MIN6 cells were divided into five groups: the control, high glucose, different dose of asprosin (50nmol/L, 100nmol/L, and 150nmol/L); or divided into four groups: the control, high glucose, vehicle, and asprosin groups. Mouse Fbn1-del pCDH-GFP-Puro vector were transfected into MIN6 cells in the asprosin group. STM2457 was served as METTL3 inhibitor.
Results
The cell viability of MIN6 cells and insulin secretion were decreased after asprosin and high glucose treatment. High glucose and asprosin incubation or transfection contributed to increased expression of caspase-1 which was assessed using immunofluorescence. In addition, the expression of NLRP3, ASC, caspase-1, and GSDMD, and the concentration of IL-1β and IL-18 were significantly increased after high glucose and asprosin incubation or transfection. Asprosin transfection increased the protein expression of METTL3. Then the effects of asprosin on the cell viability, insulin secretion, the expression of caspase-1 and pyroptosis related proteins were ameliorated significantly after inhibiting METTL3 using STM2457.
Conclusion
Asprosin induces β cell pyroptosis through METTL3-mediated m6A modification.