The Role Of CYP4A In Renal Fibrosis Induced By Unilateral Ureteral Obstruction In Mice

Objective: Renal fibrosis is a common way for CKD to progress to end-stage renal failure.It is closely related to the clinical diagnosis and treatment stage of CKD and the degree of renal function deterioration.The prognosis is very poor and the treatment methods are limited.CYP4 A,as a target gene of peroxisome proliferators-activated receptors(PPAR?),can alleviate kidney injury induced by AngII in mice.PPAR?agonists can reduce natriuretic effect by regulating CYP4 A expression in mouse kidneys.Pressure,and the role of CYP4 A in renal fibrosis remains to be studied.This study investigated the role of CYP4 A in the pathogenesis of renal fibrosis by constructing a mouse unilateral ureteral obstruction(UUO)model and intragastrically administered PPAR? agonist fenofibrate to up-regulate the expression of CYP4 A in the kidney.Methods: Thirty-one 8-week-old C57 BL / 6J mice were randomly divided into sham operation group(Sham),unilateral ureteral obstruction group(UUO)and fenofibrate treatment group(UUO + Feno);UUO group and UUO + Feno group The left ureter was ligated.In the Sham group,only the ureter was separated,and no obstruction was performed.In the UUO + Feno group,fenofibrate was administered at a dose of 10 mg / kg / d,and the other two groups were not treated with gavage.After 14 days,blood samples were taken for blood creatinine(CRE)and urea nitrogen(BUN),Hematoxylin-Eosin(H & E)staining,Masson's staining,and Sirius Red staining for pathological changes in kidney tissue.Proline content(HYP)was used to detect the HYP content in kidney tissues;immunohistochemical(IHC)method was used to detect the expression of ?-SMA and Collegan-? protein;polymerase chain reaction(Realtime PCR)method was used to detect renal fibrosis-related factors and CYP4 A mRNA expression levels;Western blot was used to detect renal fibrosis-related factors and CYP4 A protein expression levels.Results:1.Serum CRE and BUN levels in the UUO + Feno group were significantly lower than those in the UUO group(P <0.05);2.The degree of kidney injury and collagen deposition in UUO + Feno group was significantly reduced compared with that in UUO group(P <0.05);3.The content of hydroxyproline in the renal tissue of the UUO + Feno group was significantly reduced compared with theUUO group(P <0.05);4.The expression of renal fibrosis marker proteins ?-SMA and Collegan-? in the UUO + Feno group was significantly reduced compared with the UUO group(P <0.05);5.The expression of renal fibrosis-related genes in the UUO + Feno group was significantly lower than that in the UUO group,and the expression of CYP4 A gene was increased(P <0.05);6.Relative protein of ?-SMA,Collegan-?,and MMP2 proteins Compared with the UUO group,the expression level was significantly reduced,and the expression of CYP4 A protein was increased(P <0.05).Conclusions:1.Three members of mouse CYP4 A family,4A10,4A12,and 4A14,are all related to renal fibrosis;2.CYP4 A relieves renal fibrosis,and its function may be mediated by the expression of genes related to resistance to fibrosis;3.The up-regulation of CYP4 A is closely related to the improvement of renal fibrosis,which may have important guiding significance for the development of clinical treatment of renal fibrosis drugs.