Fig. 10: Corisin-induced kidney cell damage and fibrosis in diabetic chronic kidney disease and the protective potential of anticorisin monoclonal antibody.

Diabetes-associated dysbiosis increases corisin release from the microbiome into systemic circulation, where it binds to serum albumin. The corisin-albumin complex reaches the glomeruli and proximal tubular epithelial cells, binding to cubilin, an albumin receptor, and thereby facilitating corisin entry into podocytes and proximal tubular epithelial cells. Within these cells, corisin induces a senescence-associated secretory phenotype, resulting in the elevated secretion of inflammatory cytokines, chemokines, matrix metalloproteinases, and growth factors that promote inflammation, epithelial-mesenchymal transition, apoptosis of podocytes and tubular epithelial cells, myofibroblast recruitment, and extracellular matrix deposition (e.g., collagen I). Areas of the glomeruli and tubules affected by increased apoptosis are subsequently replaced by fibrotic tissue, accelerating disease progression and leading ultimately to a fatal outcome. The anti-corisin monoclonal antibody binds to corisin peptides, blocking their pro-senescence activity and mitigating disease progression. mAb, monoclonal antibody.