Figure 2.

Illustration of the potential mechanisms involved in gluten-dependent podocyte injury. (a) Normal intestinal epithelium with intact tight junctions (TJ) and intraluminal microbiota. (b) Intestinal epithelium from patients with gluten sensitivity. Upon gluten exposure, intestinal cells increase zonulin secretion, a protein that can disrupt intercellular tight junctions. (1) Elevated circulating zonulin could then have a direct effect on podocytes by disrupting their tight junctions and consequently, leading to slit diaphragm malfunction and proteinuria. (2) Alternatively, disrupted tight junctions in intestinal epithelial cells may increase the permeability of the gut, which allows toxins produced by the microbiota to enter the circulation and to activate the immune system. Subsequent cytokine production by immune cells may cause injury to podocytes in the kidney.