Role of the CCL20/CCR6 axis in tubular epithelial cell injury : Kidney-specific translational insights from acute kidney injury to chronic kidney disease
© 2024 Federation of American Societies for Experimental Biology..
This study investigated the role of the axis involving chemokine receptor 6 (CCR6) and its ligand chemokine (C-C motif) ligand 20 (CCL20) in acute kidney disease (AKD) using an ischemia-reperfusion injury (IRI) model. The model was established by clamping the unilateral renal artery pedicle of C57BL/6 mice for 30 min, followed by evaluation of CCL20/CCR6 expression at 4 weeks post-IRI. In vitro studies were conducted to examine the effects of hypoxia and H2 O2 -induced oxidative stress on CCL20/CCR6 expression in kidney tissues of patients with AKD and chronic kidney disease (CKD). Tubular epithelial cell apoptosis was more severe in C57BL/6 mice than in CCL20 antibody-treated mice, and CCR6, NGAL mRNA, and IL-8 levels were higher under hypoxic conditions. CCL20 blockade ameliorated apoptotic damage in a dose-dependent manner under hypoxia and reactive oxygen species injury. CCR6 expression in IRI mice indicated that the disease severity was similar to that in patients with the AKD phenotype. Morphometry of CCL20/CCR6 expression revealed a higher likelihood of CCR6+ cell presence in CKD stage 3 patients than in stage 1-2 patients. Kidney tissues of patients with CKD frequently contained CCL20+ cells, which were positively correlated with interstitial inflammation. CCL20/CCR6 levels were increased in fibrotic kidneys at 4 and 8 weeks after 5/6 nephrectomy. These findings suggest that modulating the CCL20/CCR6 pathway is a potential therapeutic strategy for managing the progression of AKD to CKD.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:38 |
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| Enthalten in: |
FASEB journal : official publication of the Federation of American Societies for Experimental Biology - 38(2024), 2 vom: 31. Jan., Seite e23407 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Yoo, Kyung Don [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 11.01.2024 Date Revised 05.02.2024 published: Print Citation Status MEDLINE |
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| doi: |
10.1096/fj.202301069RR |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM366882015 |
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| 100 | 1 | |a Yoo, Kyung Don |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Role of the CCL20/CCR6 axis in tubular epithelial cell injury |b Kidney-specific translational insights from acute kidney injury to chronic kidney disease |
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| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2024 Federation of American Societies for Experimental Biology. | ||
| 520 | |a This study investigated the role of the axis involving chemokine receptor 6 (CCR6) and its ligand chemokine (C-C motif) ligand 20 (CCL20) in acute kidney disease (AKD) using an ischemia-reperfusion injury (IRI) model. The model was established by clamping the unilateral renal artery pedicle of C57BL/6 mice for 30 min, followed by evaluation of CCL20/CCR6 expression at 4 weeks post-IRI. In vitro studies were conducted to examine the effects of hypoxia and H2 O2 -induced oxidative stress on CCL20/CCR6 expression in kidney tissues of patients with AKD and chronic kidney disease (CKD). Tubular epithelial cell apoptosis was more severe in C57BL/6 mice than in CCL20 antibody-treated mice, and CCR6, NGAL mRNA, and IL-8 levels were higher under hypoxic conditions. CCL20 blockade ameliorated apoptotic damage in a dose-dependent manner under hypoxia and reactive oxygen species injury. CCR6 expression in IRI mice indicated that the disease severity was similar to that in patients with the AKD phenotype. Morphometry of CCL20/CCR6 expression revealed a higher likelihood of CCR6+ cell presence in CKD stage 3 patients than in stage 1-2 patients. Kidney tissues of patients with CKD frequently contained CCL20+ cells, which were positively correlated with interstitial inflammation. CCL20/CCR6 levels were increased in fibrotic kidneys at 4 and 8 weeks after 5/6 nephrectomy. These findings suggest that modulating the CCL20/CCR6 pathway is a potential therapeutic strategy for managing the progression of AKD to CKD | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a acute kidney injury | |
| 650 | 4 | |a chemokine ligand 20 | |
| 650 | 4 | |a chemokine receptor 6 | |
| 650 | 4 | |a chronic kidney disease | |
| 650 | 4 | |a hypoxia | |
| 650 | 7 | |a Ligands |2 NLM | |
| 650 | 7 | |a CCR6 protein, human |2 NLM | |
| 650 | 7 | |a Receptors, CCR6 |2 NLM | |
| 650 | 7 | |a CCL20 protein, human |2 NLM | |
| 650 | 7 | |a Chemokine CCL20 |2 NLM | |
| 650 | 7 | |a CCR6 protein, mouse |2 NLM | |
| 700 | 1 | |a Yu, Mi-Yeon |e verfasserin |4 aut | |
| 700 | 1 | |a Kim, Kyu Hong |e verfasserin |4 aut | |
| 700 | 1 | |a Lee, Seongmin |e verfasserin |4 aut | |
| 700 | 1 | |a Park, EunHee |e verfasserin |4 aut | |
| 700 | 1 | |a Kang, Seongmin |e verfasserin |4 aut | |
| 700 | 1 | |a Lim, Doo-Ho |e verfasserin |4 aut | |
| 700 | 1 | |a Lee, Yeonhee |e verfasserin |4 aut | |
| 700 | 1 | |a Song, Jeongin |e verfasserin |4 aut | |
| 700 | 1 | |a Kown, Soie |e verfasserin |4 aut | |
| 700 | 1 | |a Kim, Yong Chul |e verfasserin |4 aut | |
| 700 | 1 | |a Kim, Dong Ki |e verfasserin |4 aut | |
| 700 | 1 | |a Lee, Jong Soo |e verfasserin |4 aut | |
| 700 | 1 | |a Kim, Yon Su |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Seung Hee |e verfasserin |4 aut | |
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