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Blockage of S100A8/A9 ameliorates septic nephropathy in mice
Septic acute kidney injury (AKI) is the commonest cause of complication of sepsis in intensive care units, but its pathophysiology remains unclear. Calprotectin (S100A8/A9), which is a damage-associated molecular patterns (DAMPs) molecule, exerts a critical role in modulating leukocyte recruitment a...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2023
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10398385/ https://www.ncbi.nlm.nih.gov/pubmed/37547329 http://dx.doi.org/10.3389/fphar.2023.1172356 |
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author | Shi, Wei Wan, Tian-Tian Li, Hui-Hua Guo, Shu-Bin |
author_facet | Shi, Wei Wan, Tian-Tian Li, Hui-Hua Guo, Shu-Bin |
author_sort | Shi, Wei |
collection | PubMed |
description | Septic acute kidney injury (AKI) is the commonest cause of complication of sepsis in intensive care units, but its pathophysiology remains unclear. Calprotectin (S100A8/A9), which is a damage-associated molecular patterns (DAMPs) molecule, exerts a critical role in modulating leukocyte recruitment and inflammatory response during various diseases. However, role of S100A8/A9 in septic AKI is largely unknown. In this research, Septic AKI was triggered by cecal ligation and puncture (CLP) operation in wild-type mice, which treated with or without an S100A9 inhibitor, Paquinimod (Paq, 10 mg/kg) that prevents S100A8/A9 to bind to Toll-like receptor 4 (TLR4). Renal function, pathological changes, cell death, and oxidative stress were evaluated. Our research indicated that the mRNA and protein expression of S100A9 are time-dependently elevated in the kidney following CLP. Moreover, the administration of Paq for 24 h significantly improved CLP-induced renal dysfunction and pathological alterations compared with vehicle treatment in mice. These beneficial effects were associated with the inhibition of CLP-triggered renal tubular epithelial cell apoptosis, inflammation, superoxide production, and mitochondrial dynamic imbalance. What’s more, we further confirmed the above findings by cell co-culture experiments. Our study demonstrates that S100A9 is a prominent protein to lead to septic AKI, and the selective inhibition of S100A9 could represent a new therapeutic approach which can treat septic AKI. |
format | Online Article Text |
id | pubmed-10398385 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-103983852023-08-04 Blockage of S100A8/A9 ameliorates septic nephropathy in mice Shi, Wei Wan, Tian-Tian Li, Hui-Hua Guo, Shu-Bin Front Pharmacol Pharmacology Septic acute kidney injury (AKI) is the commonest cause of complication of sepsis in intensive care units, but its pathophysiology remains unclear. Calprotectin (S100A8/A9), which is a damage-associated molecular patterns (DAMPs) molecule, exerts a critical role in modulating leukocyte recruitment and inflammatory response during various diseases. However, role of S100A8/A9 in septic AKI is largely unknown. In this research, Septic AKI was triggered by cecal ligation and puncture (CLP) operation in wild-type mice, which treated with or without an S100A9 inhibitor, Paquinimod (Paq, 10 mg/kg) that prevents S100A8/A9 to bind to Toll-like receptor 4 (TLR4). Renal function, pathological changes, cell death, and oxidative stress were evaluated. Our research indicated that the mRNA and protein expression of S100A9 are time-dependently elevated in the kidney following CLP. Moreover, the administration of Paq for 24 h significantly improved CLP-induced renal dysfunction and pathological alterations compared with vehicle treatment in mice. These beneficial effects were associated with the inhibition of CLP-triggered renal tubular epithelial cell apoptosis, inflammation, superoxide production, and mitochondrial dynamic imbalance. What’s more, we further confirmed the above findings by cell co-culture experiments. Our study demonstrates that S100A9 is a prominent protein to lead to septic AKI, and the selective inhibition of S100A9 could represent a new therapeutic approach which can treat septic AKI. Frontiers Media S.A. 2023-07-20 /pmc/articles/PMC10398385/ /pubmed/37547329 http://dx.doi.org/10.3389/fphar.2023.1172356 Text en Copyright © 2023 Shi, Wan, Li and Guo. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Pharmacology Shi, Wei Wan, Tian-Tian Li, Hui-Hua Guo, Shu-Bin Blockage of S100A8/A9 ameliorates septic nephropathy in mice |
title | Blockage of S100A8/A9 ameliorates septic nephropathy in mice |
title_full | Blockage of S100A8/A9 ameliorates septic nephropathy in mice |
title_fullStr | Blockage of S100A8/A9 ameliorates septic nephropathy in mice |
title_full_unstemmed | Blockage of S100A8/A9 ameliorates septic nephropathy in mice |
title_short | Blockage of S100A8/A9 ameliorates septic nephropathy in mice |
title_sort | blockage of s100a8/a9 ameliorates septic nephropathy in mice |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10398385/ https://www.ncbi.nlm.nih.gov/pubmed/37547329 http://dx.doi.org/10.3389/fphar.2023.1172356 |
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