Hepatic-specific vitamin D receptor downregulation alleviates aging-related metabolic dysfunction-associated steatotic liver disease

Figure 3 Vitamin D receptor expression in the liver increased after senescence. A: Three-month-old telomerase RNA component knockout mice (Terc^-/-) or wild-type (WT) mice were fed a methionine/choline-deficient diet for 6 weeks. The protein expression levels of P53 and vitamin D receptor (VDR) and the corresponding quantitative results, and the mRNA levels of P53 and VDR are shown; B: Two-month-old WT mice and 18-month-old WT mice were fed a standard chow diet. Protein expression levels of P53 and VDR and corresponding quantitative results, and mRNA levels of P53 and VDR; C-F: MRNA levels of VDR in AML12 or HepG2 cells after senescence was established; AML12 cells were treated with hydrogen peroxide (H₂O₂) (400 μM) for 6 hours (C); AML12 cells were irradiated with 8 Gy of X-rays (D); HepG2 cells were treated with H₂O₂ (400 μM) for 6 hours (E); HepG2 cells were irradiated with 8 Gy of X-rays (F); G: MRNA levels of P53 and VDR in AML12 or HepG2 cells treated with Nutlin-3a (10 μM) for 48 hours; H: MRNA levels of P53 and VDR in senescent AML12 or HepG2 cells treated with Nutlin-3a (10 μM) for 48 hours. Protein and mRNA levels were normalized to those of glyceraldehyde-3-phosphate dehydrogenase. The data are presented as the means ± SDs. ^aP < 0.05. ^bP < 0.01. ^cP < 0.001. P calculated according to student’s t tests. WT: Wild-type; MCD: Methionine-choline-deficient diet; H₂O₂: Hydrogen peroxide; VDR: Vitamin D receptor; GAPDH: Glyceraldehyde-3-phosphate dehydrogenase; NC: Negative control.