The Characteristics of Intestinal-Barrier Damage in Rats With IgA Nephropathy

Am J Med Sci. 2020 Mar;359(3):168-176. doi: 10.1016/j.amjms.2019.11.011. Epub 2019 Nov 30.

Abstract

Background: Intestinal-barrier damage plays an important pathogenic role in immunoglobulin A nephropathy (IgAN). In this study, we explored the characteristics of the intestinal barrier in rats with IgAN.

Materials and methods: We randomly divided 17 Sprague Dawley (SD) male rats into a normal control group (NC; n = 9) and an IgAN model group (n = 8). Feces in the distal ileum were taken for intestinal-microbiota 16sDNA sequencing. We also took a segment of terminal ileum to analyze intestinal morphology and to detect mRNA and protein expression of the tight-junction proteins zonula occludens-1 (ZO-1) and occludin (OCLN), as well as of mucin 2 (MUC2). We then measured levels of serum diamine oxidase (DAO) and D-lactic acid (D-LA), the biomarkers of intestinal permeability.

Results: Compared with the NC group, mRNA expression levels of ZO-1 (t = 4.216, P = 0.0007), OCLN (t = 2.413, P = 0.029) and MUC2 (t = 0.859, P < 0.0001) were significantly decreased in the IgAN model group. Protein expression of ZO-1 (t = 7.349, P < 0.0001) and OCLN (t = 6.367, P < 0.0001) was also decreased in the IgAN model group. Conversely, serum DAO (t = 3.758, P = 0.0024) and D-LA (t = 2.246, P = 0.0427) levels increased in this group. At the genus level, the relative abundance of Ruminococcus2 (P = 0.0086) was increased in the IgAN model group.

Conclusions: Decreased expression of ZO-1, OCLN and MUC2, plus intestinal-microbiota dysbiosis, are associated with intestinal-barrier damage in IgAN rats.

Keywords: Immunoglobulin A nephropathy; Intestinal microbiota; Intestinal mucosal immune system; Mucin; Tight-junction protein.

MeSH terms

  • Animals
  • Glomerulonephritis, IGA / physiopathology*
  • Intestinal Mucosa / physiology*
  • Intestines / physiopathology*
  • Male
  • Permeability
  • Random Allocation
  • Rats
  • Rats, Sprague-Dawley
  • Tight Junctions / physiology*