Fig. 5: FXR regulates COX6A2 expression in β-cells.
From: FXR-regulated COX6A2 triggers mitochondrial apoptosis of pancreatic β-cell in type 2 diabetes
A The potential binding site of FXR in the promoter region of Cox6a2 gene was analyzed with the bioinformatics database JASPAR. B The result of RNA-seq in islets from FXR+/+ and FXR−/− mice. C, D The expression of COX6A2 mRNA (C) and protein (D) were determined in islets from FXR+/+ and FXR−/− mice. Bars represent means ± SEM, n = 4 (C) or 3 (D). **p < 0.01 (t-test). E, F qPCR (E) and Western blotting (F) analysis of COX6A2 mRNA (E) and protein (F) expression in scramble control and sh-FXR INS-1 832/13 cells. Bars represent means ± SEM, n = 4. **p < 0.01 (t-test). G COX6A2 protein expression was determined in INS-1 832/13 cells treated with DMSO or 20 μM Z-guggulsterone (ZGS) for 48 h. Bars represent means ± SEM, n = 3. **p < 0.01 (t-test). H, I COX6A2 mRNA (H) and protein (I) were examined in islets isolated from SD rats. The rats were subjected to intraperitoneal injection of CDCA at a dose of 20 mg/kg for 2 weeks. Bars represent means ± SEM, n = 3 rats per group. *, p < 0.05; **p < 0.01 (t-test). J, K ChIP assays were performed to determine the acetylation of histone H3 at lysine 27 (J), and the occupancy of p300 (K), at the Cox6a2 promoter in the scramble and sh-FXR INS-1 832/13 cells. Bars represent means ± SEM, n = 3. *p < 0.05, **p < 0.01 (t-test). L The level of Cox6a2 mRNA was examined in the scramble and sh-FXR INS-1 832/13 cells treated with DMSO or 10 μM C646 for 48 h. Data are means ± SEM, n = 3. *p < 0.05 (t-test).
