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. 2023 May 5;24(9):8329. doi: 10.3390/ijms24098329

Figure 3.

Figure 3

Mechanisms of tissue-sodium-accumulation-induced cardiac fibrosis and peritoneal membrane dysfunction via TonEBP activation. (A) Heart; (B) peritoneal membrane. (A) High salt intake induces activation of TonEBP, which upregulates MCP-1 expression by cardiomyocytes, leading to macrophage infiltration via the TonEBP–MCP-1 pathway in CKD [50]. Macrophages express inflammatory mediators such as TNF-α, IL-6, and IL-1, leading to induction of TGF-β in inflammation during the fibrosis process [78]. TonEBP plays an important role in cardiac inflammation and cardiac fibrosis in patients with renal failure and high salt intake. (B) Excessive dietary salt intake under renal dysfunction enhances accumulation of sodium, leading to activation of TonEBP [50]. TonEBP upregulates MCP-1, inflammatory cytokines, VEGF-A, and VEGF-C in vivo. IL-6 enhances MCP-1 and VEGF-A expression [74], leading to further macrophage infiltration and angiogenesis. High-tonicity conditions upregulate expression of MCP-1, IL-6, VEGF-A, and VEGF-C by mesothelial cells and macrophages via TonEBP activation [74]. TonEBP regulates inflammatory and angiogenetic changes in the peritoneum of CKD patients. These structural changes result in peritoneal membrane dysfunction.