Abstract

Objective: IgA nephropathy has been the most common primary glomerular disease in China. This study aimed to investigate the detail molecular mechanism of intestinal flora imbalance through the LPS/TLR4 pathway to regulate IgA1 secretion to induce IgA nephropathy.

Methods: A mouse model of IgA nephropathy was established. Collect all mice blood and urine, and ELISA was also used to analyze IL-6, TNF-α, MCP-1, COX2, Gd-IgA1 level. Analyze the distribution and content of IgA+B220+B lymphocytes in all mouse intestinal tissues with tissue immunofluorescence tracking technology. HE staining was used to analyze the pathological damage characteristics of kidney tissue. Tissue immunofluorescence technique was used to analyze glomerular IgA deposition. Protein TIL4, BAFF, APRIL expression in mesenteric lymphoid tissues was detected by western blot analysis.

Results: For 5 groups of mice (normal control group + 4 experimental groups), the amount or degree of the physiological indicators and inflammatory factors detected by ELISA, B lymphocytes and IgA sedimentation measured by immunofluorescence tracing, kidney pathological detected by HE staining and the expression of immune-related proteins measured with western blotting, all showed a common trend: IgA-N group> IgA-N+GEC group> IgA-N+anti- TLR4 group> IgA-N+anti-TLR4+GEC group> NC group.

Conclusion: The TLR4 antibody and GEC for the treatment of intestinal tract regulated and repaired intestinal function, so that IgA nephritis was also relieved at the same time. The results proved the relation between the LPS/TLR4 pathway regulating mesenteric B cells to secrete low-glycosylated poly-IgA1 and IgA nephritis, which provided a new potential therapeutic plan for IgA nephritis.

Keywords: IgA nephropathy; Intestinal flora imbalance; LPS/TLR4 pathway; Mesenteric B cell