Histone deacetylase 3 regulates CIC-5 to inhibit renal fibrosis in mice with unilateral ureteral obstruction
10.3969/j.issn.1671-8348.2025.07.002
- VernacularTitle:组蛋白去乙酰化酶3调控CIC-5抑制单侧输尿管梗阻小鼠肾纤维化的机制研究
- Author:
Huiling BAI
1
;
Shixia YANG
Author Information
1. 甘肃省中医院外周血管介入科,兰州 730050
- Keywords:
histone deacetylase 3;
renal fibrosis;
ureteral obstruction;
CIC-5
- From:
Chongqing Medicine
2025;54(7):1527-1533
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the mechanism of effects of histone deacetylase 3(HDAC3)on re-nal fibrosis in mice with unilateral ureteral obstruction(UUO)by regulating CIC-5.Methods A UUO mouse model was constructed,and intervention was performed on the expression of HDAC3 and CIC-5 in mice.A UUO mouse model was constructed and the mice were divided into the following groups:sham-operated group(Sham group),UUO group(UUO model mice without any treatment),sh-NC group(UUO model mice injec-ted with sh-NC via tail vein),sh-HDAC3 group(UUO model mice injected with sh-HDAC3 via tail vein),HDAC3 overexpression group(UUO model mice injected with HDAC3 overexpression vector via tail vein),and HDAC3+CIC-5 overexpression group(UUO model mice injected with HDAC3 and CIC-5 overexpression vectors via tail vein),with 5 mice in each group.Intervention was performed on the expression of HDAC3 and CIC-5 in the mice.HE staining and Masson staining were used to detect the pathological changes of mouse kidney tissue.The expression of renal fibrosis markers(α-SMA,Collagen-Ⅰ,MMP2)in mouse kidney tissue was detected by RT-qPCR and Western blot.The levels of blood urea nitrogen(BUN)and creatinine(Cr)in the serum of mice were detected by an automatic biochemical analyzer.Results UUO mice showed obvious renal tissue damage and increased fibrosis.The mRNA and protein expression levels of CIC-5 in the renal tis-sue of the UUO group were lower than those in the Sham group,while the mRNA and protein expression lev-els of HDAC3 were higher(P<0.05).The BUN,Cr levels,and the mRNA and protein expression levels of α-SMA,Collagen-I,and MMP2 were higher in the UUO group than in the Sham group(P<0.05).The BUN,Cr levels,and the mRNA and protein expression levels of α-SMA,Collegan-Ⅰ,and MMP2 were lower in the sh-HDAC3 group than in the sh-NC group(P<0.05).The BUN,Cr levels,and the mRNA and protein ex-pression levels of α-SMA,Collegan-Ⅰ,and MMP2 were higher in the HDAC3 group than in the Sham group and UUO group(P<0.05).The BUN,Cr levels,and the mRNA and protein expression levels of α-SMA,Col-legan-Ⅰ,and MMP2 were lower in the HDAC3+CIC-5 group than in the HDAC3 group(P<0.05).Conclu-sion HDAC3 inhibits the expression of CIC-5 by regulating its acetylation,thereby promoting renal fibrosis in UUO mice.Inhibiting the expression of HDAC3 is expected to be an effective way to improve UUO renal fibrosis.
