Abstract: SA-PO611
Evaluation of the Renoprotective Role of Endogenous Galectin-3 and Mechanism in Lupus Nephritis
Session Information
- Glomerular Diseases: Immunology, Inflammation - II
November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1202 Glomerular Diseases: Immunology and Inflammation
Authors
- Yang, Shin-Ruen, National Defense Medical Center, Taipei, Taiwan, Taipei, Taiwan
- Ka, Shuk-Man, National Defense Medical Center, Taipei, Taiwan, Taipei, Taiwan
- Chung-Yao, Wu, National Defense Medical Center, Taipei, Taiwan, Taipei, Taiwan
- Chen, Ann, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taipei, Taiwan
Background
Lupus nephritis (LN) is a major complication of systemic lupus erythematosus. Current therapeutic regimens to control the acute onset of LN progression include high doses of corticosteroids, cytotoxic agents and disease-modifying antirheumatic drugs. However, there is still a major concern about the potential, systemic adverse events of these drugs. Thus, the development of pathogenic pathway-based new therapies with much fewer and more tolerable side effects is clinically warranted. Galectin-3 (Gal-3) is a β-galactoside-binding protein and implicated in diverse biological processes in macrophages, dendritic cells (DCs), activated lymphocytes, and epithelial cells. However, the role of Gal-3 and exact mechanisms involved in the development and progression/deterioration of LN has yet to be determined, although renal expression of the protein is observed in LN patients.
Methods
Gal-3 KO-Y chromosome-linked autoimmune acceleration (Yaa) mutation was introduced in KO1 strain (KO1.Yaa) mice, a spontaneous mouse model of LN, which is deficient of Gal-3 were generated to investigate the renoprotective effects of Gal-3 in two complementary LN mouse models. Moreover, lupus-like nephritis in Gal-3 KO mice induced by LPS injections. Renal function, pathology and pathogenesis-based experiments galactoside-binding.
Results
In the present study, the results show that [1] the distribution and expression levels of Gal-3 were increased in renal biopsy specimens from LN patients, compared to normal control subjects; [2] deficiency of endogenous Gal-3 resulted in markedly increased severity in clinical and pathological alterations in both the LPS-induced LN in Gal-3 KO mice and spontaneous LN in Gal-3 KO-KO1.Yaa mice, compared to their respective wild type counterparts that equally induced of or developed galactoside-binding; and [3] greatly enhanced activation of T cells and B cells as well increased monocytosis in peripheral blood mononuclear cells were observed in the spontaneous LN in Gal-3 KO-KO1.Yaa mice, compared to KO1.Yaa mice.
Conclusion
Gal-3 played a protective role in the development of LN, and justify the protein as a potential drug candidate for LN.
Funding
- Government Support - Non-U.S.