Tissue Sodium Accumulation Induces Organ Inflammation and Injury in Chronic Kidney Disease
High salt intake is a primary cause of over-hydration in chronic kidney disease (CKD) patients. Inflammatory markers are predictors of CKD mortality; however, the pathogenesis of inflammation remains unclear. Sodium storage in tissues has recently emerged as an issue of concern. The binding of sodiu...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-05-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/9/8329 |
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| author | Yasuhiko Ito Ting Sun Hiroya Tanaka Makoto Yamaguchi Hiroshi Kinashi Fumiko Sakata Shunnosuke Kunoki Yukinao Sakai Takuji Ishimoto |
| author_facet | Yasuhiko Ito Ting Sun Hiroya Tanaka Makoto Yamaguchi Hiroshi Kinashi Fumiko Sakata Shunnosuke Kunoki Yukinao Sakai Takuji Ishimoto |
| author_sort | Yasuhiko Ito |
| collection | DOAJ |
| description | High salt intake is a primary cause of over-hydration in chronic kidney disease (CKD) patients. Inflammatory markers are predictors of CKD mortality; however, the pathogenesis of inflammation remains unclear. Sodium storage in tissues has recently emerged as an issue of concern. The binding of sodium to tissue glycosaminoglycans and its subsequent release regulates local tonicity. Many cell types express tonicity-responsive enhancer-binding protein (TonEBP), which is activated in a tonicity-dependent or tonicity-independent manner. Macrophage infiltration was observed in the heart, peritoneal wall, and para-aortic tissues in salt-loading subtotal nephrectomized mice, whereas macrophages were not prominent in tap water-loaded subtotal nephrectomized mice. TonEBP was increased in the heart and peritoneal wall, leading to the upregulation of inflammatory mediators associated with cardiac fibrosis and peritoneal membrane dysfunction, respectively. Reducing salt loading by a diuretic treatment or changing to tap water attenuated macrophage infiltration, TonEBP expression, and inflammatory marker expression. The role of TonEBP may be crucial during the cardiac fibrosis and peritoneal deterioration processes induced by sodium overload. Anti-interleukin-6 therapy improved cardiac inflammation and fibrosis and peritoneal membrane dysfunction. Further studies are necessary to establish a strategy to regulate organ dysfunction induced by TonEBP activation in CKD patients. |
| first_indexed | 2024-03-11T04:15:54Z |
| format | Article |
| id | doaj.art-2472360d97044ef2a776d06f1d3bfdd1 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T04:15:54Z |
| publishDate | 2023-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-2472360d97044ef2a776d06f1d3bfdd12023-11-17T23:08:09ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-05-01249832910.3390/ijms24098329Tissue Sodium Accumulation Induces Organ Inflammation and Injury in Chronic Kidney DiseaseYasuhiko Ito0Ting Sun1Hiroya Tanaka2Makoto Yamaguchi3Hiroshi Kinashi4Fumiko Sakata5Shunnosuke Kunoki6Yukinao Sakai7Takuji Ishimoto8Department of Nephrology and Rheumatology, Aichi Medical University, Nagakute 480-1195, JapanDepartment of Nephrology and Rheumatology, Aichi Medical University, Nagakute 480-1195, JapanDepartment of Nephrology and Rheumatology, Aichi Medical University, Nagakute 480-1195, JapanDepartment of Nephrology and Rheumatology, Aichi Medical University, Nagakute 480-1195, JapanDepartment of Nephrology and Rheumatology, Aichi Medical University, Nagakute 480-1195, JapanDepartment of Nephrology, Nagoya University Graduate School of Medicine, Nagoya 464-0813, JapanDepartment of Nephrology and Rheumatology, Aichi Medical University, Nagakute 480-1195, JapanDepartment of Nephrology, Nippon Medical School, Tokyo 113-8602, JapanDepartment of Nephrology and Rheumatology, Aichi Medical University, Nagakute 480-1195, JapanHigh salt intake is a primary cause of over-hydration in chronic kidney disease (CKD) patients. Inflammatory markers are predictors of CKD mortality; however, the pathogenesis of inflammation remains unclear. Sodium storage in tissues has recently emerged as an issue of concern. The binding of sodium to tissue glycosaminoglycans and its subsequent release regulates local tonicity. Many cell types express tonicity-responsive enhancer-binding protein (TonEBP), which is activated in a tonicity-dependent or tonicity-independent manner. Macrophage infiltration was observed in the heart, peritoneal wall, and para-aortic tissues in salt-loading subtotal nephrectomized mice, whereas macrophages were not prominent in tap water-loaded subtotal nephrectomized mice. TonEBP was increased in the heart and peritoneal wall, leading to the upregulation of inflammatory mediators associated with cardiac fibrosis and peritoneal membrane dysfunction, respectively. Reducing salt loading by a diuretic treatment or changing to tap water attenuated macrophage infiltration, TonEBP expression, and inflammatory marker expression. The role of TonEBP may be crucial during the cardiac fibrosis and peritoneal deterioration processes induced by sodium overload. Anti-interleukin-6 therapy improved cardiac inflammation and fibrosis and peritoneal membrane dysfunction. Further studies are necessary to establish a strategy to regulate organ dysfunction induced by TonEBP activation in CKD patients.https://www.mdpi.com/1422-0067/24/9/8329sodium storageTonEBPinflammationorgan dysfunctionIL-6 |
| spellingShingle | Yasuhiko Ito Ting Sun Hiroya Tanaka Makoto Yamaguchi Hiroshi Kinashi Fumiko Sakata Shunnosuke Kunoki Yukinao Sakai Takuji Ishimoto Tissue Sodium Accumulation Induces Organ Inflammation and Injury in Chronic Kidney Disease International Journal of Molecular Sciences sodium storage TonEBP inflammation organ dysfunction IL-6 |
| title | Tissue Sodium Accumulation Induces Organ Inflammation and Injury in Chronic Kidney Disease |
| title_full | Tissue Sodium Accumulation Induces Organ Inflammation and Injury in Chronic Kidney Disease |
| title_fullStr | Tissue Sodium Accumulation Induces Organ Inflammation and Injury in Chronic Kidney Disease |
| title_full_unstemmed | Tissue Sodium Accumulation Induces Organ Inflammation and Injury in Chronic Kidney Disease |
| title_short | Tissue Sodium Accumulation Induces Organ Inflammation and Injury in Chronic Kidney Disease |
| title_sort | tissue sodium accumulation induces organ inflammation and injury in chronic kidney disease |
| topic | sodium storage TonEBP inflammation organ dysfunction IL-6 |
| url | https://www.mdpi.com/1422-0067/24/9/8329 |
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