ASN's Mission

To create a world without kidney diseases, the ASN Alliance for Kidney Health elevates care by educating and informing, driving breakthroughs and innovation, and advocating for policies that create transformative changes in kidney medicine throughout the world.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on X

Kidney Week

Abstract: TH-PO554

Galectin-3 Involved in the Development of IgA Nephropathy

Session Information

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.