2024/08/05
Keio University
Fukushima University
University of Shizuoka
RIKEN
A research group led by Yusuke Kinashi (a third-year student in the Ph.D. program at the Graduate School of Pharmaceutical Sciences, Keio University), Associate Professor Shunsuke Kimura, and Professor Koji Hase of the university's Faculty of Pharmacy, in collaboration with the Keio University School of Medicine, Fukushima University, the University of Shizuoka, and RIKEN, has demonstrated for the first time in a mouse model that the disruption of the intestinal epithelial barrier is a cause of the onset of IgA nephropathy. This research is an important step toward elucidating the causes of IgA nephropathy, a designated intractable disease in Japan.
The intestinal barrier function is maintained by the production of mucus and antimicrobial peptides, the secretion of IgA antibodies, and other factors. When this barrier weakens, it leads to a condition known as "leaky gut," where intestinal substances enter the body. Leaky gut has been thought to be associated with various extra-intestinal diseases, but the causal relationship has not been clear.
In this study, the researchers found that mice lacking the AP-1B complex, which is responsible for sorting and transporting proteins, in their intestinal epithelial cells exhibit characteristics of a leaky gut. Furthermore, these mice showed a significant increase in blood IgA levels, as well as the deposition of IgA in the renal glomeruli and the presence of immune complexes containing IgA with abnormal glycan modifications, which are characteristic features of IgA nephropathy. The study also revealed that the disruption of the intestinal epithelial barrier in these mice caused an imbalance in the gut microbiota (dysbiosis), and that treatment with antibiotics could reduce IgA production, improve glycan modifications, and suppress IgA deposition in the glomeruli.
This study has experimentally proven for the first time that a leaky gut is a cause of IgA nephropathy. It also suggests that controlling the gut microbiota may be an effective treatment for IgA nephropathy. Further research is expected to lead to a better understanding of the mechanisms of IgA nephropathy and the establishment of new therapeutic methods. The results of this research were published in the international academic journal "eBioMedicine" on July 25, 2024.
For the full press release, please see below.