Maresin-1 Attenuates Sepsis-Associated Acute Kidney Injury via Suppressing Inflammation, Endoplasmic Reticulum Stress and Pyroptosis by Activating the AMPK/SIRT3 Pathway
© 2024 Sun et al..
Background: Sepsis-associated acute kidney injury (SA-AKI) is a common complication in patients with sepsis, triggering high morbidity and mortality. Maresin-1 (MaR1) is a pro-resolution lipid mediator that promotes the resolution of acute inflammation and protects organs from inflammation.
Methods: In this study, we established an SA-AKI model using cecal ligation and puncture (CLP) and investigated the effect and mechanism of MaR1. The blood and kidneys were harvested 24 hours after surgery. The blood biochemical/routine indicators, renal function, SA-AKI-related pathophysiological processes, and AMPK/SIRT3 signaling in septic mice were observed by histological staining, immunohistochemical staining, Western blot, qPCR, ELISA and TUNEL Assay.
Results: MaR1 treatment alleviated kidney injury in septic mice, reflected in improved pathological changes in renal structure and renal function. MaR1 treatment decreased the levels of serum creatinine (sCr) and blood urea nitrogen (BUN) and the expressions of KIM-1, NGAL and TIMP-2, which were related to kidney injury, while inhibited the expressions of inflammatory factors TNF-α, IL-1β and IL-6. The expression of endoplasmic reticulum stress-related indicators p-PERK/PERK, GRP78, p-EIF2α/EIF2α, ATF4, CHOP, and pyroptosis-related indicators Caspase-1, NLRP3, GSDMD, IL-18, and IL-1β also decreased after MaR1 treatment. The mechanism may be related to the activation of the AMPK/SIRT3 signaling pathway, and an AMPK inhibitor (compound C) partially reverses MaR1's protective effects in septic mice.
Conclusion: Taken together, these findings suggest that MaR1 may partially ameliorate SA-AKI by activating the AMPK/SIRT3 signaling pathway, providing a potential new perspective for research on SA-AKI.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:17 |
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| Enthalten in: |
Journal of inflammation research - 17(2024) vom: 15., Seite 1349-1364 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Sun, Miaomiao [VerfasserIn] |
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| Links: |
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| Themen: |
AMPK/SIRT3 |
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| Anmerkungen: |
Date Revised 05.03.2024 published: Electronic-eCollection Citation Status PubMed-not-MEDLINE |
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| doi: |
10.2147/JIR.S442729 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM369244583 |
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| 100 | 1 | |a Sun, Miaomiao |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Maresin-1 Attenuates Sepsis-Associated Acute Kidney Injury via Suppressing Inflammation, Endoplasmic Reticulum Stress and Pyroptosis by Activating the AMPK/SIRT3 Pathway |
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| 500 | |a published: Electronic-eCollection | ||
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| 520 | |a © 2024 Sun et al. | ||
| 520 | |a Background: Sepsis-associated acute kidney injury (SA-AKI) is a common complication in patients with sepsis, triggering high morbidity and mortality. Maresin-1 (MaR1) is a pro-resolution lipid mediator that promotes the resolution of acute inflammation and protects organs from inflammation | ||
| 520 | |a Methods: In this study, we established an SA-AKI model using cecal ligation and puncture (CLP) and investigated the effect and mechanism of MaR1. The blood and kidneys were harvested 24 hours after surgery. The blood biochemical/routine indicators, renal function, SA-AKI-related pathophysiological processes, and AMPK/SIRT3 signaling in septic mice were observed by histological staining, immunohistochemical staining, Western blot, qPCR, ELISA and TUNEL Assay | ||
| 520 | |a Results: MaR1 treatment alleviated kidney injury in septic mice, reflected in improved pathological changes in renal structure and renal function. MaR1 treatment decreased the levels of serum creatinine (sCr) and blood urea nitrogen (BUN) and the expressions of KIM-1, NGAL and TIMP-2, which were related to kidney injury, while inhibited the expressions of inflammatory factors TNF-α, IL-1β and IL-6. The expression of endoplasmic reticulum stress-related indicators p-PERK/PERK, GRP78, p-EIF2α/EIF2α, ATF4, CHOP, and pyroptosis-related indicators Caspase-1, NLRP3, GSDMD, IL-18, and IL-1β also decreased after MaR1 treatment. The mechanism may be related to the activation of the AMPK/SIRT3 signaling pathway, and an AMPK inhibitor (compound C) partially reverses MaR1's protective effects in septic mice | ||
| 520 | |a Conclusion: Taken together, these findings suggest that MaR1 may partially ameliorate SA-AKI by activating the AMPK/SIRT3 signaling pathway, providing a potential new perspective for research on SA-AKI | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a AMPK/SIRT3 | |
| 650 | 4 | |a Maresin-1 | |
| 650 | 4 | |a endoplasmic reticulum stress | |
| 650 | 4 | |a inflammation | |
| 650 | 4 | |a pyroptosis | |
| 650 | 4 | |a sepsis-associated acute kidney injury | |
| 700 | 1 | |a Wang, Fuquan |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Haopeng |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Mengyu |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Yu |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Chenchen |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Yan |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Dingyu |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Jianhua |e verfasserin |4 aut | |
| 700 | 1 | |a Yao, Shanglong |e verfasserin |4 aut | |
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