Maresin-1 and its receptors RORα/LGR6 as potential therapeutic target for respiratory diseases

Zhao, Mengmeng; Li, Chenfei; Zhang, Jishou; Yin, Zheng; Zheng, Zihui; Wan, Jun; Wang, Menglong

doi:10.1016/j.phrs.2022.106337

Cited by 11 publications

(4 citation statements)

References 184 publications

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“…RORa is a recently discovered nuclear receptor of MaR1 [ 18 ]. We thus knocked out RORa in liver macrophages to explore whether the protective effects of MaR1 depended on activating RORa.…”

Section: Resultsmentioning

confidence: 99%

Maresin1 alleviates liver ischemia/reperfusion injury by reducing liver macrophage pyroptosis

Zeng

Xian

et al. 2023

J Transl Med

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Background Cell pyroptosis has a strong proinflammatory effect, but it is unclear whether pyroptosis of liver macrophages exacerbates liver tissue damage during liver ischemia‒reperfusion (I/R) injury. Maresin1 (MaR1) has a strong anti-inflammatory effect, and whether it can suppress liver macrophage pyroptosis needs further study. Methods This study aimed to investigate whether MaR1 can alleviate liver I/R injury by inhibiting macrophage pyroptosis. The effects of MaR1 on cell pyroptosis and mitochondrial damage were studied by dividing cells into control, hypoxia/reoxygenation, and hypoxia/reoxygenation + MaR1 groups. Knocking out RORa was used to study the mechanism by which MaR1 exert its protective effects. Transcriptome analysis, qRT‒PCR and Western blotting were used to analyze gene expression. Untargeted metabolomics techniques were used to analyze metabolite profiles in mice. Flow cytometry was used to assess cell death and mitochondrial damage. Results We first found that MaR1 significantly reduced liver I/R injury. We observed that MaR1 decreased liver I/R injury by inhibiting liver macrophage pyroptosis. Then, we discovered that MaR1 promotes mitochondrial oxidative phosphorylation, increases the synthesis of ATP, reduces the generation of ROS, decreases the impairment of mitochondrial membrane potential and inhibits the opening of mitochondrial membrane permeability transition pores. MaR1 inhibits liver macrophage pyroptosis by protecting mitochondria. Finally, we found that MaR1 exerts mitochondrial protective effects through activation of its nuclear receptor RORa and the PI3K/AKT signaling pathway. Conclusions During liver I/R injury, MaR1 can reduce liver macrophage pyroptosis by reducing mitochondrial damage, thereby reducing liver damage.

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“…RORa is a recently discovered nuclear receptor of MaR1 [ 18 ]. We thus knocked out RORa in liver macrophages to explore whether the protective effects of MaR1 depended on activating RORa.…”

Section: Resultsmentioning

confidence: 99%

Maresin1 alleviates liver ischemia/reperfusion injury by reducing liver macrophage pyroptosis

Zeng

Xian

et al. 2023

J Transl Med

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“… 20 Inhibition of proinflammatory macrophage polarization and/or enhancement of anti-inflammatory macrophage polarization through different pathways can significantly improve septic myocardial injury. 21 , 22 , 23 , 24 Therefore, macrophage polarization is a key factor in the occurrence and development of cardiac injury in sepsis, and finding key targets to regulate macrophage polarization is of great significance to improve myocardial injury in sepsis. In our study, we found for the first time that IL-30 ameliorated septic myocardial injury by regulating macrophage polarization, which has important clinical value.…”

Section: Discussionmentioning

confidence: 99%

IL-30 protects against sepsis-induced myocardial dysfunction by inhibiting pro-inflammatory macrophage polarization and pyroptosis

Zhao¹,

Zheng²,

Zhang³

et al. 2023

iScience

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“…Its anti-inflammatory and pro-resolution properties help to promote the resolution of acute inflammation and protect organs from inflammation. 10,11 By reducing the inflammatory response, oxidative stress, ER stress, pyroptosis, and apoptosis, these protective effects are primarily accomplished. [11][12][13][14][15] MaR1 has been thoroughly studied, but its regulatory mechanism, notably in SA-AKI, is yet unknown.…”

Section: Introductionmentioning

confidence: 99%

“…10,11 By reducing the inflammatory response, oxidative stress, ER stress, pyroptosis, and apoptosis, these protective effects are primarily accomplished. [11][12][13][14][15] MaR1 has been thoroughly studied, but its regulatory mechanism, notably in SA-AKI, is yet unknown.…”

Section: Introductionmentioning

confidence: 99%

Maresin-1 Attenuates Sepsis-Associated Acute Kidney Injury via Suppressing Inflammation, Endoplasmic Reticulum Stress and Pyroptosis by Activating the AMPK/SIRT3 Pathway

Sun,

Wang,

et al. 2024

JIR

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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.

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Maresin-1 and its receptors RORα/LGR6 as potential therapeutic target for respiratory diseases

Cited by 11 publications

References 184 publications

Maresin1 alleviates liver ischemia/reperfusion injury by reducing liver macrophage pyroptosis

Maresin1 alleviates liver ischemia/reperfusion injury by reducing liver macrophage pyroptosis

IL-30 protects against sepsis-induced myocardial dysfunction by inhibiting pro-inflammatory macrophage polarization and pyroptosis

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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