The apoptosis clearance signal phosphatidylserine inhibits leukocyte migration and promotes inflammation resolution in vivo

Bet, Ângela Cristina; Justina, Ana Maria Della; Ramos, Gustavo; Assreuy, Jamil

doi:10.1016/j.ejphar.2020.173095

Cited by 13 publications

(5 citation statements)

References 26 publications

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“…As illustrated in Figures 3(a) – 3(d) , GO enrichment analysis suggested that for BP, DEGs were significantly enriched in the following processes, e.g., leukocyte migration and cell-cell adhesion, response to steroid hormone, and positive regulation of leukocyte activation and inflammatory response, related to inflammation [ 18 ]. For CC, DEGs were significantly enriched in vesicle lumen and granule lumen which were related with cell adhesion and migration [ 19 ].…”

Section: Resultsmentioning

confidence: 99%

Optical Coherence Tomography Angiography Characteristics Serve as Retinal Vein Occlusion Therapeutic Biomarkers for Dexamethasone Intravitreal Implant

2021

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Background. Retinal vein occlusion (RVO) is the second most common vision-threatening retinal vascular disease. Intravitreal dexamethasone implant has been applied to treat macular edema secondary to RVO (RVO-ME). However, the alteration of morphologic features detected with optical coherence tomography angiography (OCTA) has not been fully studied in RVO-ME patients before and after the treatment. Objective. This study is aimed at identifying potential therapeutic targets in RVO with integrative bioinformatic analysis and compares the OCTA characteristics alterations in patients with RVO-ME receiving injection of dexamethasone intravitreal implant. Methods. Bioinformatic analysis was analyzed in GSE101398 dataset from the Gene Expression Omnibus database. Multiple functional enrichment analyses were performed, and protein-protein interaction network was constructed to visualize the key node genes. Eleven eyes with RVO-ME were examined with OCTA before and after intravitreal dexamethasone implant. The OCTA parameters, including macular thickness, vessel density, foveal avascular zone parameters, the number of hyperreflective foci (HRF), area of cystoid edema, and subretinal fluid (SRF), were compared. The correlation was analyzed between best-corrected visual acuity (BCVA) and OCTA parameters. Results. A total of 79 differentially expressed genes were identified. Functional enrichment analyses revealed the enriched inflammatory events in RVO. In RVO-ME, Pearson correlation revealed that baseline BCVA was positively correlated with the area of SRF and central macular thickness, while no correlation was detected between baseline BCVA and HRF number or the area of cystoid edema. The visual acuity improved, and the central macular thickness was decreased after intravitreal dexamethasone implant injection. Besides, the number of HRF, the area of cystoid edema, and SRF were significantly alleviated after dexamethasone intravitreal injection. Conclusion. Retinal inflammation plays a crucial role in RVO pathogenesis. The imaging biomarkers of RVO including Müller glial intracellular edema, and retinal pigment epithelium dysfunction, could be assessed in OCTA and attenuated by intravitreal dexamethasone implant effectively.

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Section: Resultsmentioning

confidence: 99%

Optical Coherence Tomography Angiography Characteristics Serve as Retinal Vein Occlusion Therapeutic Biomarkers for Dexamethasone Intravitreal Implant

2021

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“…Intact plasma membrane microcapsules and lipid rafts are the important molecular basis for signal transduction, especially transmembrane signal transduction [ 27 ]. Emerging evidence reveals that the production of phosphatidylserine, “apoptosis clearance signaling”, inhibits leukocyte migration and promotes inflammation resolution [ 28 ]. As a cofactor, phosphatidylserine is required for the activation of the TAM family, and further plays a counter-inflammation response in macrophages [ 29 , 30 ].…”

Section: Discussionmentioning

confidence: 99%

Serinc2 deficiency causes susceptibility to sepsis-associated acute lung injury

et al. 2022

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Background Severe sepsis and its subsequent complications cause high morbidity and mortality rates worldwide. The lung is one of the most vulnerable organs sensitive to the sepsis-associated inflammatory storm and usually develops into acute respiratory distress syndrome (ARDS)/acute lung injury (ALI). The pathogenesis of sepsis-associated ALI is accompanied by coordinated transmembrane signal transduction and subsequent programmed cell death; however, the underlying mechanism remains largely unclear. Results Here we find that the expression of serine incorporator 2 (Serinc2), a protein involved in phosphatidylserine synthesis and membrane incorporation, is upregulated in cecal ligation and puncture (CLP)-induced ALI. Furthermore, the Serinc2-knockout (KO) mouse line is generated by the CRISPR-cas9 approach. Compared with wild-type mice, the Serinc2-KO mice exhibit exacerbated ALI-related pathologies after CLP. The expressions of pro-inflammatory factors, including IL1β, IL6, TNFα, and MCP1, are significantly enhanced by Serinc2 deficiency, concurrent with over-activation of STAT3, p38 and ERK pathways. Conversely, Serinc2 overexpression in RAW264.7 cells significantly suppresses the inflammatory responses induced by lipopolysaccharide (LPS). Serinc2 KO aggravates CLP-induced apoptosis as evidenced by increases in TUNEL-positive staining, Bax expression, and cleaved caspase-3 and decreases in BCL-2 expression and Akt phosphorylation, whereas these changes are suppressed by Serinc2 overexpression in LPS-treated RAW264.7 cells. Moreover, the administration of AKTin, an inhibitor of Akt, abolishes the protective effects of Serinc2 overexpression against inflammation and apoptosis. Conclusions Our findings demonstrate a protective role of Serinc2 in the lung through activating the Akt pathway, and provide novel insight into the pathogenesis of sepsis-induced ALI.

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“…Binding of Tim-3 and CEACAM1 promotes temporal differences in Restimulation-induced cell death (RICD) sensitivity in the effector T cell response [ 35 ], which plays a key role in regulating anti-tumour immunity [ 34 ] and antiviral responses [ 36 ]. As another Tim-3 ligand, phosphatidylserine (PtdSer) may play a crucial role in regulating tolerance by clearing apoptotic cells [ 37 , 38 ] and enhancing cross-antigen presentation [ 39 ]. High mobility group protein B1 (HMGB1) known to be a DNA binding protein was identified as the ligand of Tim-3.…”

Section: Discussionmentioning

confidence: 99%

Expression changes of Tim-3 as one of supplementary indicators for monitoring prognosis of liver pathological changes in chronic HBV infection

Du²,

Lou

et al. 2022

BMC Infect Dis

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Purpose This study was designed to analyze the liver tissue changes among the CHB patients who received treatment for at least 6 months and follow-up for at least 1 year, together with the correlation between the different disease condition and serum markers. Methods One-hundred and eighty-five CHB patients underwent antiviral therapy for at least 6 months were enrolled. In the 12-month follow-up, ultrasonography-guided biopsy was performed. The patients were grouped based on the serum markers and pathological changes in liver tissues. Then we determined the serum markers, virological tests and Tim-3 expression among these groups. Results Antiviral therapy significantly reduced liver inflammation indicators and serum Tim-3 level. However, the fibrosis process of liver tissue was not changed, and there are still disputes on the serum marker and hepatic lesion outcomes. Under normal liver function or negative hepatitis B e antigen (HBeAg) of CHB patients, there might be consensus between Tim-3 change and liver pathological outcome. According to the liver tissue inflammation and fibrosis conditions, Tim-3 was positively correlated with liver function indices. Besides, it was also related to fibrosis stage and inflammation grade. Conclusion There were inconsistent changes between serum markers and liver tissue conditions after anti-viral therapy. Tim-3 expression was more suitable to indicate the changes of liver inflammatory and fibrosis response to some extent than ALT and AST. It may serve as a certain indicator to predict the CHB prognosis, which could be used as one of the monitoring indicators in liver pathological changes of chronic HBV infection, especially in monitoring liver tissue inflammation.

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The apoptosis clearance signal phosphatidylserine inhibits leukocyte migration and promotes inflammation resolution in vivo

Cited by 13 publications

References 26 publications

Optical Coherence Tomography Angiography Characteristics Serve as Retinal Vein Occlusion Therapeutic Biomarkers for Dexamethasone Intravitreal Implant

Optical Coherence Tomography Angiography Characteristics Serve as Retinal Vein Occlusion Therapeutic Biomarkers for Dexamethasone Intravitreal Implant

Serinc2 deficiency causes susceptibility to sepsis-associated acute lung injury

Expression changes of Tim-3 as one of supplementary indicators for monitoring prognosis of liver pathological changes in chronic HBV infection

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