The Potential Role of NFAT5 and Osmolarity in Peritoneal Injury

Figure 1

Involvement of osmotic and nonosmotic mechanism in peritoneal fibrosis. (1) Rise in osmolarity stimulates NFAT5 in patients with “uremia.” Activation of NFAT5 results in a counterregulatory response protecting cells from hyperosmolarity but also induces inflammatory mediators (e.g., the chemokine CCL2) and growth factors. Additionally antifibrotic factors are downregulated. (2) Exposure to hyperosmolar dialysate might perpetuate NFAT5 induction. The balance between pro- and antifibrotic factors is shifted towards matrix deposition. Note that there are osmotic and nonosmotic factors inducing NFAT5 and also direct inducers of CCL2, which increases the complexity of the system and might lead to several vicious cycles promoting injury. Abbreviations: TNF-α = tumor necrosis factor α, Ang II = angiotensin II, PDGF-BB = platelet derived growth factor BB, TGF-β = transforming growth factor b, CCL2 = chemokine (C-C motif) ligand 2, MMP9 = matrix metalloproteinase 9, AGE = advanced glycation end products, NFAT5 = nuclear factor of activated T cells 5, and Il-1β = interleukin-1β.