Ganoderma leucocontextum attenuates acute kidney injury in mice via in-hibiting Axin2/β-catenin signaling pathway
10.3969/j.issn.1000-4718.2024.11.012
- VernacularTitle:白肉灵芝通过抑制Axin2/β-catenin信号通路减轻小鼠急性肾损伤
- Author:
Luoning ZHANG
1
;
Yaxin LI
;
Rui QIAN
;
Bengui YE
;
Qiaolan WANG
;
Tianyun HAN
;
Linshen XIE
Author Information
1. 四川大学华西公共卫生学院/华西第四医院职业病中毒科/肾脏内科,四川 成都 610041
- Keywords:
Ganoderma leucocontextum;
acute kidney injury;
inflammation;
Axin2/β-catenin signaling path-way
- From:
Chinese Journal of Pathophysiology
2024;40(11):2081-2089
- CountryChina
- Language:Chinese
-
Abstract:
AIM:To investigate the effect of Ganoderma leucocontextum extract(GLE)on mice with cisplatin-induced acute kidney injury(AKI)and lipopolysaccharide(LPS)-induced cellular inflammation.METHODS:Eight-week-old male C57BL/6 mice were randomly divided into control group,AKI group,low-dose(100 mg/kg)GLE group,high-dose(300 mg/kg)GLE group,and quercetin(100 mg/kg)group,with 6 mice in each group.The AKI model was es-tablished by intraperitoneal injection of a 20 mg/kg cisplatin solution.After GLE intervention for 3 d,serum creatinine(SCr)and blood urea nitrogen(BUN)levels were measured.Renal pathology was observed using HE and PAS staining.The expression of β-catenin and Axin2 protein in each group was detected by immunohistochemistry.The expression lev-els of interleukin-1β(IL-1β),IL-6,β-catenin and Axin2 in each group were detected by Western blot and RT-qPCR.The TCMK1 cells were stimulated with 2 mg/L LPS to simulate cellular inflammatory injury.After GLE treatment(0.2,0.4,0.6 and 0.8 g/L)for 24 h,the expressions of IL-1β,IL-6,β-catenin and Axin2 in each group were detected.Fur-ther overexpression of Axin2 was used to verify the changes in the above-mentioned indices.RESULTS:High doses of GLE significantly reduced SCr(P<0.01)and BUN(P<0.05)levels compared with the AKI mice.AKI mice showed re-nal tubule dilatation,tubular epithelial cell necrosis,vacuolation,and other pathological manifestations,which were im-proved after GLE intervention.Immunohistochemistry showed increased expression of Axin2 and β-catenin protein in the kidneys of AKI mice,which was reduced by GLE intervention.Western blot and RT-qPCR results in vitro and in vivo showed that GLE intervention significantly inhibited the expression and mRNA levels of IL-1β,IL-6,Axin2 and β-catenin(P<0.05).Overexpression of Axin2 antagonized the effect of GLE on IL-1β,IL-6,Axin2 and β-catenin,resulting in sig-nificantly up-regulated expressions of these proteins and mRNAs(P<0.01).CONCLUSION:GLE significantly allevi-ates the inflammatory response in AKI mice and LPS-induced cells,and protects against cisplatin-induced kidney injury in mice by inhibiting the Axin2/β-catenin signaling pathway.
