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Abstract: FR-PO681

Toll-Like Receptors (TLRs) Regulate the Production of Galactose-Deficient IgA1 in Human Renal Mesangial Cells

Session Information

Category: Glomerular Diseases

  • 1401 Glomerular Diseases: From Inflammation to Fibrosis

Authors

  • Deng, Zhenling, Peking University Third Hospital, Beijing, China
  • Wang, Yue, Peking University Third Hospital, Beijing, China
Background

Galactose-deficient IgA1 (Gd-IgA1) is the core factor in the pathogenesis of IgA nephropathy (IgAN). Our group found that glomerular mesangial cells (GMC) could express and secrete IgA1. The aim of this study is to investigate whether Gd-IgA1 can be expressed in normal cultured GMC, upregulated by pathogenic factors, and to explore the regulatory mechanisms between Gd-IgA1 production and pathogen infection.

Methods

Immunofluorescence and western blot were used to confirm Gd-IgA1 expression under normal or stimulated condition. RT-PCR was used to verify the TLRs transcripts.

Results

In this study, we confirmed that Gd-IgA1 can be produced and secreted by mesangial cell lines under normal culture condition, and significantly increased by staphylococcus aureus (SAC), staphylococcal enterotoxin B (SEB), lipopolysaccharide (LPS) and angiotensin II (Ang II). Evidently, SAC and SEB promoted secretion and extracellular granular deposition of Gd-IgA1 in mesangial cells, consistent with renal pathology. Interestingly, mesangial cells constitutively expressed multiple TLRs, and that engagement of mesangial cell TLRs led to produce of Gd-IgA1 and release of proinflammatory cytokines, which can be inhibited by specific repressor of TLRs.

Conclusion

In short, we reported, for the first time, that mesangial cells can produce Gd-IgA1 and regulated by TLRs. This discovery subverted our current understanding for the pathogenesis mechanism of IgAN and hopefully change the current lack of effective treatment for IgAN.

Funding

  • Government Support – Non-U.S.