A Sphingosine-1-Phosphate Modulator Ameliorates Polycystic Kidney Disease in Han:SPRD Rats

doi:10.1159/000502855

	A Sphingosine-1-Phosphate Modulator Ameliorates Polycystic Kidney Disease in Han:SPRD Rats
	Li, Xin 1,2,6; Wu, Ming 2,7; Chen, Limin 3,4; Lu, Junyan 3; Li, Guo 5; Fu, Lili 2; Qi, Na 2; Lin, Ye 2; Sun, Zhongya 4; Wang, Xueqi 2
刊名	AMERICAN JOURNAL OF NEPHROLOGY
	2020
卷号	51 期号:1 页码:1-10
关键词	FTY720 Sphingosine-1-phosphate Cordyceps sinensis Autosomal dominant polycystic kidney disease Inflammation
ISSN号	0250-8095
DOI	10.1159/000502855
通讯作者	Mei, Chang-Lin(chlmei1954@126.com)
英文摘要	Background: Inflammation plays an important role in polycystic kidney disease (PKD). Cordyceps sinensis, a prized -Chinese medicinal herb, exerts anti-tumor, anti-inflammatory and anti-metastatic effects and benefits patients with kidney diseases. The aim of this study was to test the efficacy of FTY720, an immunosuppressant derived from C. sinensis, in a rat cystic kidney disease model, and explore its underlining mechanism. Methods: Male wild type and Cy/+ Han:SPRD rats were treated with FTY720 at 3 and 10 mg/kg/day for 5 weeks and 12 weeks by gavage. Blood and kidney were collected for functional, morphological, RNA, and protein analysis. Results: Inflammation is activated in Cy/+ Han:SPRD rats. Inflammatory cytokines including interleukin 6 and tumor necrosis factor alpha were upregulated and inflammation-related pathways were activated, such as nuclear factor kappa B and signal transducer and activator of transcription 3 (STAT3) pathways. Furthermore, the bioactive sphingolipid mediator sphingosine-1-phosphate (S1P), a regulator of inflammation, was accumulated in the Cy/+ Han:SPRD rats. FTY720 significantly reduced cyst growth and delayed disease progression by reducing the accumulation of S1P, thereby inhibiting inflammatory responses. Conclusion: FTY720 treatment reduced the expression of inflammatory cytokines and attenuated the activation of NK-kappa B and STAT3 pathways in Cy/+ Han:SPRD rats. It suggests that FTY720 may serve as a therapeutic agent for clinical autosomal dominant PKD treatment.
资助项目	Ministry of Science and Technology of China[2015CB910304] ; Hi-Tech Research and Development Program of China[2012AA020302] ; Scientific Research Foundation of Shanghai Municipal Commission of Health and Family Planning[201740193] ; National Natural Science Foundation of China[91029704] ; National Natural Science Foundation of China[21472208] ; National Natural Science Foundation of China[91229204] ; National Natural Science Foundation of China[81100482] ; National Natural Science Foundation of China[81470914] ; National Natural Science Foundation of China[31371172]
WOS关键词	CYST GROWTH ; INFLAMMATION ; NRF2 ; ACTIVATION ; CORDYCEPS ; MODEL ; PATHOGENESIS ; INHIBITION ; EXPRESSION ; STRESS
WOS研究方向	Urology & Nephrology
语种	英语
出版者	KARGER
WOS记录号	WOS:000507890600001
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/282423]
专题	中国科学院上海药物研究所
通讯作者	Mei, Chang-Lin
作者单位	1.Shanghai Jiao Tong Univ, Sch Med, Shanghai Ninth Peoples Hosp, Unit Crit Nephrol, Shanghai, Peoples R China 2.Shanghai Changzheng Hosp, Div Nephrol, Fcngyang Rd 415, Shanghai 200003, Peoples R China 3.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai, Peoples R China 4.Nanchang Univ, Affiliated Hosp 1, Ctr Expt Med, Nanchang, Jiangxi, Peoples R China 5.411th Hosp PLA, Dept Orthoped, Shanghai, Peoples R China 6.Shanghai Jiao Tong Univ, Sch Med, Shanghai Ninth Peoples Hosp, Div Nephrol, Shanghai, Peoples R China 7.Shanghai Univ Tradit Chinese Med, Shuguang Hosp,Shanghai Key Lab Tradit Chinese Cli, Dept Nephrol,Key Lab Liver & Kidney Dis,Minist Ed, TCM Inst Kidney Dis,Shanghai Univ Tradit Chinese, Shanghai, Peoples R China
推荐引用方式 GB/T 7714	Li, Xin,Wu, Ming,Chen, Limin,et al. A Sphingosine-1-Phosphate Modulator Ameliorates Polycystic Kidney Disease in Han:SPRD Rats[J]. AMERICAN JOURNAL OF NEPHROLOGY,2020,51(1):1-10.
APA	Li, Xin.,Wu, Ming.,Chen, Limin.,Lu, Junyan.,Li, Guo.,...&Luo, Cheng.(2020).A Sphingosine-1-Phosphate Modulator Ameliorates Polycystic Kidney Disease in Han:SPRD Rats.AMERICAN JOURNAL OF NEPHROLOGY,51(1),1-10.
MLA	Li, Xin,et al."A Sphingosine-1-Phosphate Modulator Ameliorates Polycystic Kidney Disease in Han:SPRD Rats".AMERICAN JOURNAL OF NEPHROLOGY 51.1(2020):1-10.