RETRACTED: Complement C3 promotes islet β-cell dedifferentiation by activating Wnt/β-catenin pathway

Year: 2024

Type: article

Abstract: Islet β-cell dedifferentiation is a key step in the progression of diabetes, and complement C3 enhances secretion of several inflammatory mediators and cytokines in type 2 diabetes mellitus (T2DM). Here, we identified the underlying mechanisms of complement C3 in islet β-cell dedifferentiation. The protein level of C3 is increased in blood of T2DM patients and mice, as well as in T2DM islet β cells. Insulin, gliclazide, and metformin decreased complement C3, Nga3, and Oct4 levels but increased Pdx1 and MafA expressions; these treatments inhibit islet β-cell dedifferentiation in in vitro and in vivo models. We also observed that C3 promoted islet β-cell dedifferentiation, whereas C3 knockdown inhibited β-cell dedifferentiation. Moreover, C3 activates Wnt/β-catenin pathway by upregulating p-β-catenin levels, Wnt/β-catenin inhibitors significantly blocked C3-induced upregulation of islet β-cell dedifferentiation. In conclusion, C3 promoted islet β-cell dedifferentiation by activation of Wnt/β-catenin in T2DM. Targeting C3 might be a potential therapeutic strategy for T2DM treatment.

Source: iScience

DOI: 10.1016/j.isci.2024.111064