title: FTY720 Attenuates Angiotensin II-Induced Podocyte Damage via Inhibiting Inflammatory Cytokines.
abstract: FTY720, a new chemical substance derived from the ascomyceteIsaria sinclairii, is used for treating multiple sclerosis, renal cancer, and asthma. Sphingosine 1-phosphate (S1P) is a bioactive sphingolipid metabolite and exists in red blood cells. FTY720 is a synthetic S1P analog which can block S1P evoking physiological effects. Recently studies show that S1P was participating in activated inflammation cells induced renal injury. The objective of this study was to assess the protective effect of FTY720 on kidney damage and the potential mechanism of FTY720 which alleviate podocyte injury in chronic kidney disease. In this study, we selected 40 patients with IgA nephropathy and examined their clinical characteristics. Ang II-infusion rat renal injury model was established to evaluate the glomeruli and tubulointerstitial lesion. The result showed that the concentration of S1P in serum and urine was positively correlated with IgA nephropathy patients' renal injury. FTY720 could reduce renal histological lesions induced by Ang II-infusion in rats. Moreover, FTY720 decreased S1P synthesis in Ang II-infusion rats via downregulation of inflammatory cytokines including TNF-αand IL-6. In addition, FTY720 alleviated exogenous S1P-induced podocyte damage. In conclusion, FTY720 is able to attenuate S1P-induced podocyte damage via reducing inflammatory cytokines.
authors.affiliation: Department of Nephrology, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan 430060, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Su
authors.affiliation: Department of Nephrology, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan 430060, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Zeng
authors.affiliation: Department of Nephrology, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan 430060, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Liang
authors.affiliation: First School of Clinical Medicine, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan 430060, China.
authors.forename: Zhengyu
authors.initials: Z
authors.lastname: Luo
authors.affiliation: Department of Nephrology, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan 430060, China.
authors.forename: Yiman
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Nephrology, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan 430060, China.
authors.forename: Xifeng
authors.initials: X
authors.lastname: Lv
authors.affiliation: Department of Nephrology, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan 430060, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Han
authors.affiliation: Department of Nephrology, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan 430060, China.
authors.forename: Miao
authors.initials: M
authors.lastname: Yan
authors.affiliation: Department of Nephrology, Renmin Hospital of Wuhan University, 238 Jiefang Road, Wuhan 430060, China.
authors.forename: Cheng
authors.identifier: 0000-0002-0223-1051
authors.initials: C
authors.lastname: Chen
mesh_terms: D000328:Adult; D000804:Angiotensin II / Q000633:toxicity*; D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D000068876:Fingolimod Hydrochloride / Q000494:pharmacology* / Q000627:therapeutic use*; D006801:Humans; D007150:Immunohistochemistry; D015850:Interleukin-6 / Q000097:blood; D008246:Lysophospholipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D050199:Podocytes / Q000187:drug effects* / Q000378:metabolism*; D011863:Radioimmunoassay; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000188:drug therapy / Q000378:metabolism; D013110:Sphingosine / Q000031:analogs & derivatives / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D014945:Wound Healing / Q000187:drug effects; D055815:Young Adult
chemical_list: D015850:Interleukin-6; D008246:Lysophospholipids; D014409:Tumor Necrosis Factor-alpha; D000804:Angiotensin II; C060506:sphingosine 1-phosphate; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine