Xin Li1,2, Ming Wu1,3, Limin Chen4,5, Junyan Lu4, Guo Li6, Lili Fu1, Na Qi1, Ye Lin1, Zhongya Sun5, Xueqi Wang1, Hao Zhang4, Jingqiu Liu4, Hualiang Jiang4, Lin Li1, Chang-Lin Mei7, Cheng Luo4. 1. Division of Nephrology, Shanghai Changzheng Hospital, Shanghai, China. 2. Division of Nephrology and Unit of Critical Nephrology, Shanghai Ninth People's Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, China. 3. Department of Nephrology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine (TCM), TCM institute of Kidney Disease, Shanghai University of Traditional Chinese Medicine, Key Laboratory of Liver and Kidney Diseases, Ministry of Education, Shanghai Key Laboratory of Traditional Chinese Clinical Medicine, Shanghai, China. 4. State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China. 5. Center For Experimental Medicine, The First Affiliated Hospital of Nanchang University, Nanchang, China. 6. Department of Orthopedics, 411th Hospital of PLA, Shanghai, China. 7. Division of Nephrology, Shanghai Changzheng Hospital, Shanghai, China, chlmei1954@126.com.
Abstract
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 κB 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-κB and STAT3 pathways in Cy/+ Han:SPRD rats. It suggests that FTY720 may serve as a therapeutic agent for clinical autosomal dominant PKD treatment.
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 ratcystic 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 κB 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-κB and STAT3 pathways in Cy/+ Han:SPRD rats. It suggests that FTY720 may serve as a therapeutic agent for clinical autosomal dominant PKD treatment.
Authors: David M Levine; Stuart R Lipsitz; Zoe Co; Wenyu Song; Patricia C Dykes; Lipika Samal Journal: J Gen Intern Med Date: 2020-12-03 Impact factor: 5.128
Authors: Masaw Akbari; Jonathan D West; Nicholas Doerr; Kevin R Kipp; Neda Marhamati; Sabrina Vuong; Yidi Wang; Markus M Rinschen; Jeffrey J Talbot; Oliver Wessely; Thomas Weimbs Journal: Proc Natl Acad Sci U S A Date: 2022-07-22 Impact factor: 12.779