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Galectin-3 contributes to pathogenesis of IgA nephropathy.
Chou, Yu-Ling; Chen, Hung-Lin; Hsu, Bang-Gee; Yang, Chih-Yu; Chen, Cheng-Hsu; Lee, Yu-Ching; Tsai, I-Lin; Sung, Chih-Chien; Wu, Chia-Chao; Yang, Shin-Ruen; Suzuki, Yusuke; Yates, Edwin; Hua, Kuo-Feng; Yu, Lu-Gang; Liu, Fu-Tong; Chen, Ann; Ka, Shuk-Man.
Afiliación
  • Chou YL; Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan.
  • Chen HL; Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
  • Hsu BG; Division of Nephrology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan; School of Medicine, Tzu Chi University, Hualien, Taiwan.
  • Yang CY; Division of Nephrology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Institute of Clinical Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
  • Chen CH; Division of Nephrology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.
  • Lee YC; TMU Research Center of Cancer Translational Medicine, Taipei Medical University, Taipei, Taiwan.
  • Tsai IL; Department of Biochemistry and Molecular Cell Biology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
  • Sung CC; Division of Nephrology, Department of Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
  • Wu CC; Division of Nephrology, Department of Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
  • Yang SR; Graduate Institute of Aerospace and Undersea Medicine, Department of Medicine, National Defense Medical Center, Taipei, Taiwan.
  • Suzuki Y; Department of Nephrology, Juntendo University Faculty of Medicine, Tokyo, Japan.
  • Yates E; Department of Biochemistry and Systems Biology, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK.
  • Hua KF; Department of Biotechnology and Animal Science, National Ilan University, Ilan, Taiwan.
  • Yu LG; Department of Biochemistry and Systems Biology, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK.
  • Liu FT; Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
  • Chen A; Department of Pathology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan; Taiwan Autoantibody Biobank Initiative, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan; Graduate Institute of Medical Sciences, National Defense Medical Center, Ta
  • Ka SM; Graduate Institute of Aerospace and Undersea Medicine, Department of Medicine, National Defense Medical Center, Taipei, Taiwan. Electronic address: shukmanka@gmail.com.
Kidney Int ; 106(4): 658-670, 2024 Oct.
Article en En | MEDLINE | ID: mdl-39084257
ABSTRACT
IgA nephropathy (IgAN) is the most common type of glomerulonephritis that frequently progresses to kidney failure. However, the molecular pathogenesis underlying IgAN remains largely unknown. Here, we investigated the role of galectin-3 (Gal-3), a galactoside-binding protein in IgAN pathogenesis, and showed that Gal-3 expression by the kidney was significantly enhanced in patients with IgAN. In both TEPC-15 hybridoma-derived IgA-induced, passive, and spontaneous "grouped" ddY IgAN models, Gal-3 expression was clearly increased with disease severity in the glomeruli, peri-glomerular regions, and some kidney tubules. Gal-3 knockout (KO) in the passive IgAN model had significantly improved proteinuria, kidney function and reduced severity of kidney pathology, including neutrophil infiltration and decreased differentiation of Th17 cells from kidney-draining lymph nodes, despite increased percentages of regulatory T cells. Gal-3 KO also inhibited the NLRP3 inflammasome, yet it enhanced autophagy and improved kidney inflammation and fibrosis. Moreover, administration of 6-de-O-sulfated, N-acetylated low-molecular-weight heparin, a competitive Gal-3 binding inhibitor, restored kidney function and improved kidney lesions in passive IgAN mice. Thus, our results suggest that Gal-3 is critically involved in IgAN pathogenesis by activating the NLRP3 inflammasome and promoting Th17 cell differentiation. Hence, targeting Gal-3 action may represent a new therapeutic strategy for treatment of this kidney disease.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Ratones Noqueados / Galectina 3 / Modelos Animales de Enfermedad / Células Th17 / Proteína con Dominio Pirina 3 de la Familia NLR / Glomerulonefritis por IGA Idioma: En Revista: Kidney Int Año: 2024 Tipo del documento: Article País de afiliación: Taiwán Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Ratones Noqueados / Galectina 3 / Modelos Animales de Enfermedad / Células Th17 / Proteína con Dominio Pirina 3 de la Familia NLR / Glomerulonefritis por IGA Idioma: En Revista: Kidney Int Año: 2024 Tipo del documento: Article País de afiliación: Taiwán Pais de publicación: Estados Unidos