Maresin conjugates in tissue regeneration 1 prevents lipopolysaccharide-induced cardiac dysfunction through improvement of mitochondrial biogenesis and function

Yang, Yi; Zhu, Yinmeng; Xiao, Ji; Tian, Yang; Ma, Minqi; Li, Xinyu; Li, Fulin; Zhang, Puhong; Li, Ming; Wang, Jianguang; Jin, Shudong

doi:10.1016/j.bcp.2020.114005

Cited by 32 publications

(27 citation statements)

References 44 publications

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“…Patients with SIC typically exhibit ventricular dilatation, reduced ventricular contractility, and/or both right and left ventricular dysfunction with a reduced response to volume infusion (2,29). We previously demonstrated that cardiac function in mice decreased most significantly at 6 and 12 h after intraperitoneal injection of LPS, and then gradually recovered (22). Here, we found that post-treatment with MCTR1 6 h after LPS treatment markedly reduced the left ventricular end-systolic volume and increased the left ventricular fractional shortening, left ventricular ejection fraction.…”

Section: Discussionmentioning

confidence: 99%

“…Ethanol was blown away by nitrogen before use, and MCTR1 was dissolved rapidly in sterile saline to the desired concentration. In the MCTR1 groups, mice received MCTR1 (0.15 nmol/mouse) intravenously via the caudal vein 6 h after LPS stimulation as previously described (22). The dose of MCTR1 was selected based on previous studies (22,23).…”

Section: Methodsmentioning

confidence: 99%

“…We previously demonstrated that cardiac function was decreased after LPS administration and peaked at 6 and 12 h after challenge (22). To verify whether MCTR1 can promote cardiac function recovery from damages of LPS, mice received MCTR1 6 h after administration with LPS.…”

Section: Post-treatment With Mctr1 Improved Cardiac Function In Lps-induced Cardiac Injurymentioning

confidence: 99%

“…Previous investigations indicated that the IL-17 signaling pathway might involve the inflammation resolving work of SPMs in myocardial infarction and allergic airway inflammation (19)(20)(21). In our previous study, we found that maresin conjugates in tissue regeneration 1 (MCTR1), a newly identified SPM, could reduce lipopolysaccharide (LPS)-induced cardiac injury by upregulating mitochondrial biosynthesis and improve the survival rate (22). The mechanism of SPMs on sepsisinduced cardiac dysfunction is not clear, and whether the IL-17 signaling pathway is engaged is also unknown.…”

Section: Introductionmentioning

confidence: 99%

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γδ T/Interleukin-17A Contributes to the Effect of Maresin Conjugates in Tissue Regeneration 1 on Lipopolysaccharide-Induced Cardiac Injury

Yang¹,

Li²,

Li³

et al. 2021

Front. Immunol.

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The mechanisms underlying sepsis-induced cardiomyopathy (SIC) remain poorly understood, and there are no specific therapeutics for SIC. We investigated the effects of maresin conjugates in tissue regeneration 1 (MCTR1) on SIC and explored its potential mechanisms. The experiments were conducted using an endotoxemia model induced by lipopolysaccharide (LPS). Mice were given MCTR1 intravenously 6 h after LPS stimulation. Echocardiography was performed to assess cardiac function 12 h after LPS administration. Treatment with MCTR1 significantly enhanced cardiac function and reduced LPS-induced increase of mRNA expression levels of inflammation cytokines. Transcriptomic analysis indicated that MCTR1 inhibited neutrophil chemotaxis via the IL-17 signaling pathway. We confirmed that MCTR1 reduced the expressions of neutrophil chemoattractants and neutrophil infiltration in the LPS-stimulated hearts. MCTR1 also resulted in a considerable reduction in IL-17A production mainly derived from γδ T cells. Moreover, our results provided the first evidence that neutralizing IL-17A or depletion of γδ T cells markedly decreased neutrophil recruitment and enhanced cardiac function in LPS-induced cardiac injury. These results suggest that MCTR1 alleviates neutrophil infiltration thereby improves cardiac function in LPS-induced cardiac injury via the IL-17 signaling pathway. Thus, MCTR1 represented a novel therapeutic strategy for patients with SIC.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Post-treatment With Mctr1 Improved Cardiac Function In Lps-induced Cardiac Injurymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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γδ T/Interleukin-17A Contributes to the Effect of Maresin Conjugates in Tissue Regeneration 1 on Lipopolysaccharide-Induced Cardiac Injury

Yang¹,

Li²,

Li³

et al. 2021

Front. Immunol.

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“…7 It has been reported that MCTR1 accelerated the resolution of inflammation induced by LPS in mice, improved lung alveolar fluid clearance and restored cardiac function. [8][9][10] However, the effect of MCTR1 on pulmonary fibrosis is not well undefined.…”

Section: Introductionmentioning

confidence: 99%

MCTR1 Intervention Reverses Experimental Lung Fibrosis in Mice

Pan¹,

Li²,

Wang³

et al. 2021

JIR

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Pulmonary fibrosis (PF) is a progressing lethal disease, effective curative therapies remain elusive and mortality remains high. Maresin conjugates in tissue regeneration 1 (MCTR1) is a DHA-derived lipid mediator promoting inflammation resolution produced in macrophage. However, the effect of MCTR1 on PF remains unknown. Material and Methods: We established a lung fibrosis model in mice induced by intratracheal administration of bleomycin (BLM). On day 7 after lung fibrosis model establishment, treatment with MCTR1 up to day 21. The body weight of each mouse was recorded every day and survival curves were plotted. Histological staining was used to detect pulmonary inflammation and fibrosis. Lung sections were examined with transmission electron microscope to evaluate the ultrastructure of cells and deposit of collagen. Inflammatory cytokines in lung tissues were tested by ELISA. q-PCR and Western blot were used to evaluate the mRNA and the protein levels of EMT-related markers. Results: We found that MCTR1 intervention attenuated BLM-induced lung inflammatory and fibrotic response. Furthermore, MCTR1 protected BLM-induced epithelial cell destroy and reversed epithelial-to-mesenchymal transition phenotype into an epithelial one in lung fibrosis mice. Most importantly, post-treatment with MCTR1 restored BLM-induced lung dysfunction and enhanced survival rate significantly. Conclusion:Posttreatment with MCTR1 attenuated BLM-induced inflammation and fibrosis changes in mice, suggested MCTR1 may serve as a novel therapeutic strategy for fibrosisrelated diseases.

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Stereochemistry and functions of the new cysteinyl‐resolvin, 4S,5R‐RCTR1, in efferocytosis and erythrophagocytosis of human senescent erythrocytes

et al. 2023

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Specialized pro‐resolving lipid mediators play key functions in the resolution of the acute inflammatory response. Herein, we elucidate the stereochemical structure of the new 4S,5R‐RCTR1, a cysteinyl‐resolvin, recently uncovered in human leukocytes incubated with a 4S,5S‐epoxy‐resolvin intermediate, using liquid chromatography–tandem mass spectrometry (LC–MS/MS) and ultra‐violet (UV) spectrophotometry. With this approach, the physical properties of the new mediator prepared by total organic synthesis were matched to enzymatically produced biogenic material. In addition, we confirmed the potent biological actions of 4S,5R‐RCTR1 with human M2‐like macrophage phagocytosis of live bacteria, efferocytosis of apoptotic neutrophils, and erythrophagocytosis of senescent human red blood cells in a concentration‐dependent manner from 0.1 to 10 nM. Taken together, these results establish the complete stereochemistry of 4S,5R‐RCTR1 as 5R‐glutathionyl‐4S,17S‐dihydroxy‐6E,8E,10Z,13Z,15E,19Z‐docosahexaenoic acid and give evidence of its novel bioactivities in human phagocyte responses. Moreover, they confirm and extend the stereoselective functions of the 4S,5R‐RCTR1 with isolated human phagocytes of interest in the resolution of inflammation.

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Maresin conjugates in tissue regeneration 1 prevents lipopolysaccharide-induced cardiac dysfunction through improvement of mitochondrial biogenesis and function

Cited by 32 publications

References 44 publications

γδ T/Interleukin-17A Contributes to the Effect of Maresin Conjugates in Tissue Regeneration 1 on Lipopolysaccharide-Induced Cardiac Injury

γδ T/Interleukin-17A Contributes to the Effect of Maresin Conjugates in Tissue Regeneration 1 on Lipopolysaccharide-Induced Cardiac Injury

MCTR1 Intervention Reverses Experimental Lung Fibrosis in Mice

Stereochemistry and functions of the new cysteinyl‐resolvin, 4S,5R‐RCTR1, in efferocytosis and erythrophagocytosis of human senescent erythrocytes

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