title: FTY720, a sphingosine-1 phosphate receptor modulator, improves liver fibrosis in a mouse model by impairing the motility of bone marrow-derived mesenchymal stem cells.
abstract: FTY720 is a novel immunosuppressant that modulates sphingosine 1-phosphate (S1P) receptors for the treatment of several diseases. Several hallmarks of liver fibrosis are influenced by S1P, and the interference of S1P signaling by treatment with FTY720 results in beneficial effects in various animal models of fibrosis. However, whether these treatment strategies suppress liver fibrosis progression is incompletely understood. Here, we investigated the effects and mechanisms by which FTY720 improves liver fibrosis in the carbon tetrachloride (CCl4)-induced mouse model. FTY720 treatment significantly attenuated the expression of fibrotic markers in the injured liver of both wild-type and SCID-beige mice. The migration of bone marrow-derived mesenchymal stem cells (BMSCs) to circulation, and subsequently the injured liver, was suppressed by FTY720. Furthermore, in vitro, phosphorylated-FTY720 blocked the migration of BMSCs mediated by S1P. Thus, FTY720 is an effective therapy for liver fibrosis via the suppression of BMSC migration in the CCl4-induced mouse model.
authors.affiliation: Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, China, kongyaxian@gmail.com.
authors.forename: Yaxian
authors.initials: Y
authors.lastname: Kong
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.forename: Shuling
authors.initials: S
authors.lastname: Wang
authors.forename: Na
authors.initials: N
authors.lastname: Tang
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology* / Q000187:drug effects; D002251:Carbon Tetrachloride / Q000737:chemistry; D002465:Cell Movement; D004195:Disease Models, Animal; D005355:Fibrosis / Q000378:metabolism / Q000473:pathology; D000068876:Fingolimod Hydrochloride; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000188:drug therapy*; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects; D051379:Mice; D008813:Mice, Inbred ICR; D016513:Mice, SCID; D011409:Propylene Glycols / Q000494:pharmacology*; D049349:Receptors, Lysosphingolipid / Q000378:metabolism*; D015398:Signal Transduction; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D014945:Wound Healing
chemical_list: D007166:Immunosuppressive Agents; D011409:Propylene Glycols; D049349:Receptors, Lysosphingolipid; D002251:Carbon Tetrachloride; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine