Blockade of the mTOR signaling pathway with rapamycin ameliorates aristolochic acid nephropathy

doi:10.3892/etm.2020.8550

科研成果详情

题名	Blockade of the mTOR signaling pathway with rapamycin ameliorates aristolochic acid nephropathy
作者	Wu, Minmin1; Tang, Lili 2; Chen, Bicheng1; Zheng, Jianjian1; Dong, Fengquan 3; Su, Zhen1; Lin, Fan1,3
发表日期	2020-04
发表期刊	EXPERIMENTAL AND THERAPEUTIC MEDICINE 影响因子和分区
语种	英语
原始文献类型	Article
关键词	aristolochic acid nephropathy mTOR signaling pathway rapamycin apoptosis proliferation interstitial fibrosis
其他关键词	TUBULAR EPITHELIAL-CELLS ; P70 S6 KINASE ; MESENCHYMAL TRANSITION ; RENAL INJURY ; APOPTOSIS ; REGULATORS ; MECHANISM ; FIBROSIS
摘要	Chronic aristolochic acid nephropathy (CAAN) is characterized by widespread apoptosis and interstitial fibrosis, which severely impairs kidney function. mTOR is crucial for cell proliferation and protein synthesis. In the present study, the therapeutic effects of blockade of mTOR activity by rapamycin on aristolochic acid nephropathy were investigated. In vitro experiments to determine cell apoptosis and cell cycle alterations caused by aristolochic acid (AA)-induced injury were conducted on three groups of cells: Untreated control, AAI (treated with aristolochic acid I), and AAI + rapamycin (RMS). In vivo experiments were conducted in a CAAN mouse model. One group of mice was treated with AAI (the CAAN group), while another group was treated with AAI and rapamycin (the treatment group). Kidney function and pathological changes in these mice were assessed by serum creatinine and urea nitrogen analysis. Hematoxylin and eosin staining of renal tissue was performed to evaluate the treatment effects of rapamycin. Western blotting and immunohistochemical staining were used to explore the mechanisms by which rapamycin inhibited cell proliferation, apoptosis and tissue fibrosis. In the in vitro experiments, rapamycin prevented AAI-induced cell apoptosis and G(2)/M checkpoint cell cycle arrest. In the in vivo experiments, the treatment group exhibited lower serum creatinine and urea nitrogen, less extensive tubular atrophy and increased amount of glomerulus. Additionally, western blotting and immunohistochemical staining showed that the treatment group exhibited decreased expression levels of fibrosis-, proliferation- and apoptosis-related proteins compared with the CAAN group. The findings suggest that rapamycin can ameliorate kidney injury induced by AAI via blockade of mTOR, and thus could be a therapeutic strategy for patients with CAAN.
资助项目	Natural Science Foundation of Zhejiang ProvinceNatural Science Foundation of Zhejiang Province [LY14H050006]; National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [8157080113]; Natural Science Foundation of Shenzhen University General Hospital [SUGH2018QD013]
出版者	SPANDIDOS PUBL LTD
出版地	ATHENS
ISSN	1792-0981
EISSN	1792-1015
卷号	19 期号:4 页码:2887-2894
DOI	10.3892/etm.2020.8550
页数	8
WOS类目	Medicine, Research & Experimental
WOS研究方向	Research & Experimental Medicine
WOS记录号	WOS:000523637100060
收录类别	SCIE ; PUBMED
URL	查看原文
Pubmed记录号	32256773
PMC记录号	PMC7086201
通讯作者地址	[Lin, Fan]Shenzhen Univ, Dept Nephrol, Gen Hosp, 1098 Xueyuan Rd, Shenzhen 518055, Guangdong, Peoples R China.
引用统计	被引频次：1[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/4915
专题	第一临床医学院（信息与工程学院）、附属第一医院_浙江省胰脏肝脏危重性疾病重点实验室附属第一医院
通讯作者	Lin, Fan
作者单位	1.Wenzhou Med Univ, Key Lab Diag & Treatment Severe Hepatopancreat Di, Affiliated Hosp 1, Wenzhou 325000, Zhejiang, Peoples R China; 2.Chinese Med Hosp Jining, Clin Lab, Jining 272037, Shandong, Peoples R China; 3.Shenzhen Univ, Dept Nephrol, Gen Hosp, 1098 Xueyuan Rd, Shenzhen 518055, Guangdong, Peoples R China
第一作者单位	附属第一医院
第一作者的第一单位	附属第一医院
推荐引用方式 GB/T 7714	Wu, Minmin,Tang, Lili,Chen, Bicheng,et al. Blockade of the mTOR signaling pathway with rapamycin ameliorates aristolochic acid nephropathy[J]. EXPERIMENTAL AND THERAPEUTIC MEDICINE,2020,19(4):2887-2894.
APA	Wu, Minmin., Tang, Lili., Chen, Bicheng., Zheng, Jianjian., Dong, Fengquan., ... & Lin, Fan. (2020). Blockade of the mTOR signaling pathway with rapamycin ameliorates aristolochic acid nephropathy. EXPERIMENTAL AND THERAPEUTIC MEDICINE, 19(4), 2887-2894.
MLA	Wu, Minmin,et al."Blockade of the mTOR signaling pathway with rapamycin ameliorates aristolochic acid nephropathy".EXPERIMENTAL AND THERAPEUTIC MEDICINE 19.4(2020):2887-2894.