Abstract: TH-PO554
Galectin-3 Involved in the Development of IgA Nephropathy
Session Information
- Glomerular Diseases: From Inflammation to Fibrosis - I
November 02, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1401 Glomerular Diseases: From Inflammation to Fibrosis
Authors
- Ka, Shuk-Man, National Defense Medical Center, Taipei, Taiwan
- Chou, Yu-Ling, National Defense Medical Center, Taipei, Taiwan
- Chen, Ann, Hualien Tzu Chi Hospital Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan
Background
IgA nephropathy (IgAN) is the most common type of glomerulonephritis that frequently progresses to end-stage renal disease. However, the molecular pathogenesis underlying IgAN remains largely unknown. This study investigated the role of galectin-3 (Gal-3), a galactoside-binding protein in IgAN pathogenesis.
Methods
Two complementary mouse IgAN models, a model induced with TEPC-15 hybridoma using Gal-3 knockout (KO) mice, and a spontaneous IgAN model of “grouped” ddY (gddY) mice were employed.
Results
Gal-3 expression increased with disease severity in the glomeruli, peri-glomerular regions, and some renal tubules in both the inducible and spontaneous IgAN models. Gal-3 KO in the TEPC-15 hybridoma-induced IgAN mice significantly improved proteinuria and renal function and reduced severity of renal pathology, including neutrophil infiltration and decreased differentiation of Th17 cells from renal-draining lymph nodes, despite increased percentages of regulatory T cells. Gal-3 KO also inhibited the NLRP3 inflammasome, yet it enhanced autophagy and improved renal inflammation and fibrosis. Moreover, administration of 6-de-O-sulfated, N-acetylated low-molecular-weight heparin, a competitive Gal-3 binding inhibitor, restored renal function and improved renal lesions in passive IgAN mice.
Conclusion
These results suggest that Gal-3 is critically involved in IgAN pathogenesis by activating the NLRP3 inflammasome and promoting Th17 cell differentiation. Therefore, targeting Gal-3 action may represent a new therapeutic strategy for treatment of this renal disease.