Iguratimod prevents renal fibrosis in unilateral ureteral obstruction model mice by suppressing M2 macrophage infiltration and macrophage-myofibroblast transition.

Publisher: Informa Healthcare Country of Publication: England NLM ID: 8701128 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1525-6049 (Electronic) Linking ISSN: 0886022X NLM ISO Abbreviation: Ren Fail Subsets: MEDLINE

Publication: London : Informa Healthcare
Original Publication: New York, N.Y. : M. Dekker, c1987-

Ureteral Obstruction*/complications ; Macrophages*/drug effects ; Disease Models, Animal* ; Fibrosis* ; Sulfonamides*/pharmacology ; Sulfonamides*/therapeutic use ; Interleukin-4*/metabolism ; STAT6 Transcription Factor*/metabolism; Animals ; Mice ; Male ; Myofibroblasts/drug effects ; Chromones/pharmacology ; Chromones/therapeutic use ; Kidney/pathology ; Signal Transduction/drug effects ; Transforming Growth Factor beta/metabolism ; Kidney Diseases/etiology ; Kidney Diseases/prevention & control ; Kidney Diseases/pathology ; Kidney Diseases/drug therapy ; Mice, Inbred C57BL ; Immunosuppressive Agents/pharmacology

Iguratimod is a novel synthetic, small-molecule immunosuppressive agent used to treat rheumatoid arthritis. Through ongoing exploration of its role and mechanisms of action, iguratimod has been observed to have antifibrotic effects in the lung and skin; however, its effect on renal fibrosis remains unknown. This study aimed to investigate whether iguratimod could affect renal fibrosis progression. Three different concentrations of iguratimod (30 mg/kg/day, 10 mg/kg/day, and 3 mg/kg/day) were used to intervene in unilateral ureteral obstruction (UUO) model mice. Iguratimod at 10 mg/kg/day was observed to be effective in slowing UUO-mediated renal fibrosis. In addition, stimulating bone marrow-derived macrophages with IL-4 and/or iguratimod, or with TGF-β and iguratimod or SRC inhibitors in vitro , suggested that iguratimod mitigates the progression of renal fibrosis in UUO mice, at least in part, by inhibiting the IL-4/STAT6 signaling pathway to attenuate renal M2 macrophage infiltration, as well as by impeding SRC activation to reduce macrophage-myofibroblast transition. These findings reveal the potential of iguratimod as a treatment for renal disease.

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Keywords: Iguratimod; macrophage infiltration; macrophage–myofibroblast transition; renal fibrosis; unilateral ureteral obstruction

4IHY34Y2NV (iguratimod)
0 (Sulfonamides)
207137-56-2 (Interleukin-4)
0 (STAT6 Transcription Factor)
0 (Chromones)
0 (Stat6 protein, mouse)
0 (Transforming Growth Factor beta)
0 (Il4 protein, mouse)
0 (Immunosuppressive Agents)

Date Created: 20240426 Date Completed: 20240426 Latest Revision: 20240501

20250114

PMC11057400

10.1080/0886022X.2024.2327498

38666363