Maresin 1 Mitigates Sepsis-Associated Acute Kidney Injury in Mice via Inhibition of the NF-κB/STAT3/MAPK Pathways
Acute kidney injury (AKI) is one of the most common and serious complications of sepsis in which the inflammatory cascade plays a crucial role. There is now increasing evidence that lipid mediators derived from the omega-3 fatty acid docosahexaenoic acid (DHA) have potent anti-inflammatory effects t...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-11-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fphar.2019.01323/full |
| _version_ | 1811206985322856448 |
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| author | ShuJun Sun ShuJun Sun JiaMei Wang JingXu Wang JingXu Wang FuQuan Wang FuQuan Wang ShangLong Yao ShangLong Yao HaiFa Xia HaiFa Xia |
| author_facet | ShuJun Sun ShuJun Sun JiaMei Wang JingXu Wang JingXu Wang FuQuan Wang FuQuan Wang ShangLong Yao ShangLong Yao HaiFa Xia HaiFa Xia |
| author_sort | ShuJun Sun |
| collection | DOAJ |
| description | Acute kidney injury (AKI) is one of the most common and serious complications of sepsis in which the inflammatory cascade plays a crucial role. There is now increasing evidence that lipid mediators derived from the omega-3 fatty acid docosahexaenoic acid (DHA) have potent anti-inflammatory effects that promote the timely regression of acute inflammation. In this study, we investigated the protective effects and molecular mechanism of a novel DHA-derived lipid mediator Maresin 1 (MaR1) on AKI in septic mice. The cecal ligation and puncture (CLP) was used to establish a sepsis mice model. As a result, we found that MaR1 significantly increased the 7-day survival rate of septic mice and the anti-inflammatory factor IL-10 while reducing bacterial load and pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β). In addition, MaR1 dose dependently reduced renal injury scores and serum creatinine and urea nitrogen levels in septic mice while inhibiting renal neutrophil infiltration and myeloperoxidase (MPO) activity. In terms of signaling pathway, we found that MaR1 inhibits the expression of phosphorylated p65, Stat3, JNK, ERK, and p38 and significantly reduces nuclear translocation of p65. In conclusion, our results indicate that MaR1 is able to reduce neutrophil infiltration and inhibit nuclear factor-kappa B/signal transducer and activator of transcriptor 3/mitogen-activated protein kinase (NF-κB/STAT3/MAPK) activity and regulate inflammatory cytokine level to inhibit inflammatory response and thereby weaken sepsis-associated AKI in mice. |
| first_indexed | 2024-04-12T03:56:21Z |
| format | Article |
| id | doaj.art-98e65724da1f4adb8ddfe9a772c0c720 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-04-12T03:56:21Z |
| publishDate | 2019-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-98e65724da1f4adb8ddfe9a772c0c7202022-12-22T03:48:49ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122019-11-011010.3389/fphar.2019.01323482950Maresin 1 Mitigates Sepsis-Associated Acute Kidney Injury in Mice via Inhibition of the NF-κB/STAT3/MAPK PathwaysShuJun Sun0ShuJun Sun1JiaMei Wang2JingXu Wang3JingXu Wang4FuQuan Wang5FuQuan Wang6ShangLong Yao7ShangLong Yao8HaiFa Xia9HaiFa Xia10Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaInstitute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaCollege of Life and Health Sciences, Northeastern University, Shenyang, ChinaDepartment of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaInstitute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaInstitute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaInstitute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaDepartment of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaInstitute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, ChinaAcute kidney injury (AKI) is one of the most common and serious complications of sepsis in which the inflammatory cascade plays a crucial role. There is now increasing evidence that lipid mediators derived from the omega-3 fatty acid docosahexaenoic acid (DHA) have potent anti-inflammatory effects that promote the timely regression of acute inflammation. In this study, we investigated the protective effects and molecular mechanism of a novel DHA-derived lipid mediator Maresin 1 (MaR1) on AKI in septic mice. The cecal ligation and puncture (CLP) was used to establish a sepsis mice model. As a result, we found that MaR1 significantly increased the 7-day survival rate of septic mice and the anti-inflammatory factor IL-10 while reducing bacterial load and pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β). In addition, MaR1 dose dependently reduced renal injury scores and serum creatinine and urea nitrogen levels in septic mice while inhibiting renal neutrophil infiltration and myeloperoxidase (MPO) activity. In terms of signaling pathway, we found that MaR1 inhibits the expression of phosphorylated p65, Stat3, JNK, ERK, and p38 and significantly reduces nuclear translocation of p65. In conclusion, our results indicate that MaR1 is able to reduce neutrophil infiltration and inhibit nuclear factor-kappa B/signal transducer and activator of transcriptor 3/mitogen-activated protein kinase (NF-κB/STAT3/MAPK) activity and regulate inflammatory cytokine level to inhibit inflammatory response and thereby weaken sepsis-associated AKI in mice.https://www.frontiersin.org/article/10.3389/fphar.2019.01323/fullMaresin 1Sepsisacute kidney injuryinflammatorycecal ligation and puncture |
| spellingShingle | ShuJun Sun ShuJun Sun JiaMei Wang JingXu Wang JingXu Wang FuQuan Wang FuQuan Wang ShangLong Yao ShangLong Yao HaiFa Xia HaiFa Xia Maresin 1 Mitigates Sepsis-Associated Acute Kidney Injury in Mice via Inhibition of the NF-κB/STAT3/MAPK Pathways Frontiers in Pharmacology Maresin 1 Sepsis acute kidney injury inflammatory cecal ligation and puncture |
| title | Maresin 1 Mitigates Sepsis-Associated Acute Kidney Injury in Mice via Inhibition of the NF-κB/STAT3/MAPK Pathways |
| title_full | Maresin 1 Mitigates Sepsis-Associated Acute Kidney Injury in Mice via Inhibition of the NF-κB/STAT3/MAPK Pathways |
| title_fullStr | Maresin 1 Mitigates Sepsis-Associated Acute Kidney Injury in Mice via Inhibition of the NF-κB/STAT3/MAPK Pathways |
| title_full_unstemmed | Maresin 1 Mitigates Sepsis-Associated Acute Kidney Injury in Mice via Inhibition of the NF-κB/STAT3/MAPK Pathways |
| title_short | Maresin 1 Mitigates Sepsis-Associated Acute Kidney Injury in Mice via Inhibition of the NF-κB/STAT3/MAPK Pathways |
| title_sort | maresin 1 mitigates sepsis associated acute kidney injury in mice via inhibition of the nf κb stat3 mapk pathways |
| topic | Maresin 1 Sepsis acute kidney injury inflammatory cecal ligation and puncture |
| url | https://www.frontiersin.org/article/10.3389/fphar.2019.01323/full |
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