Apelin inhibits the transition of acute kidney injury to chronic kidney disease by regulating Sirt3 expression
10.12007/j.issn.0258-4646.2025.04.005
- VernacularTitle:多肽apelin通过调节去乙酰化酶Sirt3表达抑制急性肾损伤向慢性肾脏病转化
- Author:
Liyan WANG
1
;
Yiming GUAN
1
;
Zongli DIAO
1
;
Hongdong HUANG
1
Author Information
1. 首都医科大学附属北京友谊医院肾内科,北京 100050
- Publication Type:Journal Article
- Keywords:
polypeptide;
apelin;
deacetylase;
Sirt3;
acute kidney injury;
chronic kidney disease
- From:
Journal of China Medical University
2025;54(4):312-317
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the mechanism by which apelin inhibits the transition from acute kidney injury(AKI)to chronic kidney disease(CKD).Methods Human proximal tubular epithelial cells were cultured in vitro and divided into control,cisplatin,cisplatin+apelin,cisplatin+apelin+Sirt3 siRNA,and apelin groups.Cells were transfected with Sirt3 siRNA and incubated with a medium containing cisplatin(10 μmol/L)and/or apelin-13(1 μmol/L).Mitochondrial morphology was observed using MitoTracker? probes;mito-chondrial membrane potential was detected using the JC-1 assay kit;and the expression of the fibrogenic cytokine,transforming growth factor β1(TGF-β1)was measured by Western blotting.Forty 10-week-old male C57BL/6J mice were divided into control,cisplatin,cisplatin+apelin,cisplatin+apelin+Sirt3 knockdown,and empty adenovirus groups,with eight mice per group.Except for the control and empty adenovirus groups,all the other groups were intraperitoneally injected with cisplatin(20 mg/kg)to establish the AKI model.The cis-platin+apelin group was intraperitoneally injected with apelin-13(0.1 μg·kg-1·d-1);the control group was injected with an equal volume of saline;the cisplatin+apelin+Sirt3 knockdown group was injected with Sirt3 knockdown adenovirus(2 × 109 pfu/mL)via the tail vein and intraperitoneal injection of apelin-13(0.1 μg·kg-1·d-1);and the empty adenovirus group was injected with adenovirus(2 × 109 pfu/mL)via the tail vein.The mice were sacrificed after 2 weeks.Kidney fibrosis was assessed by Masson's trichome staining.Type Ⅰ collagen(Col-Ⅰ)expression was observed by immunohistochemical staining.Plasma creatinine(Cr)and blood urea nitrogen(BUN)levels were measured by ELISA.Results In vitro experiments showed that,compared with the control group,the cisplatin group exhibited reduced mitochondrial fluorescence staining,decreased mitochondrial membrane potential,and increased TGF-β1 expression(all P＜0.05).Compared with the cisplatin group,the cisplatin+apelin group showed increased fluorescence staining,elevated mitochondrial membrane potential,and reduced TGF-β1 expression(all P＜0.05);however,these effects were counteracted after Sirt3 siRNA transfection.In vivo experiments showed that,compared with the control group,the cisplatin group exhibited significant renal tubular atrophy and interstitial fibrosis,increased Col-Ⅰ positive expression,and elevated plasma Cr and BUN levels(all P＜0.05).Compared with the cisplatin group,the cisplatin+apelin group showed a significant improvement in all the above indicators(all P＜0.05).Compared with the cisplatin+apelin group,the cisplatin+apelin+Sirt3 knockdown group showed a significant reduction in the renal protective effects of apelin.Conclusion The polypeptide apelin inhibits the transition from AKI to CKD by regulating Sirt3 expression to maintain mitochondrial structure and function,which can reduce renal fibrosis and improve renal function.
