scholarly journals Endothelial Microparticles in Uremia: Biomarkers and Potential Therapeutic Targets

Toxins ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 267 ◽  
Author(s):  
Giane Favretto ◽  
Regiane Stafim da Cunha ◽  
Maria Aparecida Dalboni ◽  
Rodrigo Bueno de Oliveira ◽  
Fellype de Carvalho Barreto ◽  
...  
Keyword(s):  
Biochemical Markers ◽  
Cell Adhesion Molecule ◽  
Biological Effects ◽  
Therapeutic Targets ◽  
Kidney Dysfunction ◽  
Endothelial Microparticles ◽  
Physiological Conditions ◽  
Cell Adhesion Molecule 1 ◽  
The Impact ◽  
Intercellular Cell Adhesion Molecule

Endothelial microparticles (EMPs) are vesicles derived from cell membranes, which contain outsourced phosphatidylserine and express adhesion molecules, such as cadherin, intercellular cell adhesion molecule-1 (ICAM-1), E-selectin, and integrins. EMPs are expressed under physiological conditions and continue circulating in the plasma. However, in pathologic conditions their levels increase, and they assume a pro-inflammatory and pro-coagulant role via interactions with monocytes; these effects are related to the development of atherosclerosis. Chronic kidney dysfunction (CKD) characterizes this dysfunctional scenario through the accumulation of uremic solutes in the circulating plasma, whose toxicity is related to the development of cardiovascular diseases. Therefore, this review aims to discuss the formation of EMPs and their biological effects in the uremic environment. Data from previous research demonstrate that uremic toxins are closely associated with the activation of inflammatory biomarkers, cardiovascular dysfunction processes, and the release of EMPs. The impact of a decrease in circulating EMPs in clinical studies has not yet been evaluated. Thus, whether MPs are biochemical markers and/or therapeutic targets has yet to be established.

scholarly journals Homophilic adhesion and CEACAM1-S regulate dimerization of CEACAM1-L and recruitment of SHP-2 and c-Src

2009 ◽  
Vol 187 (4) ◽  
pp. 569-581 ◽  
Author(s):  
Mario M. Müller ◽  
Esther Klaile ◽  
Olga Vorontsova ◽  
Bernhard B. Singer ◽  
Björn Öbrink
Keyword(s):  
Cell Adhesion ◽  
Cell Adhesion Molecule ◽  
Resonance Energy Transfer ◽  
Resonance Energy ◽  
Supramolecular Organization ◽  
Transmembrane Signaling ◽  
Physiological Conditions ◽  
Allosteric Mechanism ◽  
Cell Adhesion Molecule 1 ◽  
Homophilic Adhesion

Carcinoembryonic antigen (CEA)–related cell adhesion molecule 1 (CAM1 [CEACAM1]) mediates homophilic cell adhesion and regulates signaling. Although there is evidence that CEACAM1 binds and activates SHP-1, SHP-2, and c-Src, knowledge about the mechanism of transmembrane signaling is lacking. To analyze the regulation of SHP-1/SHP-2/c-Src binding, we expressed various CFP/YFP-tagged CEACAM1 isoforms in epithelial cells. The supramolecular organization of CEACAM1 was examined by cross-linking, coclustering, coimmunoprecipitation, and fluorescence resonance energy transfer. SHP-1/SHP-2/c-Src binding was monitored by coimmunoprecipitation and phosphotyrosine-induced recruitment to CEACAM1-L in cellular monolayers. We find that trans-homophilic CEACAM1 binding induces cis-dimerization by an allosteric mechanism transmitted by the N-terminal immunoglobulin-like domain. The balance of SHP-2 and c-Src binding is dependent on the monomer/dimer equilibrium of CEACAM1-L and is regulated by trans-binding, whereas SHP-1 does not bind under physiological conditions. CEACAM1-L homodimer formation is reduced by coexpression of CEACAM1-S and modulated by antibody ligation. These data suggest that transmembrane signaling by CEACAM1 operates by alteration of the monomer/dimer equilibrium, which leads to changes in the SHP-2/c-Src–binding ratio.

scholarly journals H19 Overexpression Improved Efficacy of Mesenchymal Stem Cells in Ulcerative Colitis by Modulating the miR-141/ICAM-1 and miR-139/CXCR4 Axes

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Ming-li Zhao ◽  
Tao Chen ◽  
Teng-hui Zhang ◽  
Feng Tian ◽  
Xiao Wan
Keyword(s):  
Ulcerative Colitis ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cell Adhesion Molecule ◽  
Therapeutic Effects ◽  
Regulatory Relationship ◽  
Chemokine Receptor 4 ◽  
Cell Adhesion Molecule 1 ◽  
Relationship Of ◽  
Intercellular Cell Adhesion Molecule

Overexpression of C-X-C motif chemokine receptor 4 (CXCR4) and intercellular cell adhesion molecule-1 (ICAM-1) may promote homing of mesenchymal stem cells (MSC). In this study, we treated ulcerative colitis animals with MSC preconditioned with or without H19 and compared the therapeutic effect of MSC and MSC-H19. We evaluated the regulatory relationship of H19 vs. miR-141/miR-139 and miR-141/miR-139 vs. ICAM-1/CXCR4. We established an ulcerative colitis mouse model to assess the effect of MSC and MSC-H19. H19 was found to bind to miR-141 and miR-139. The activity of H19 was strongly decreased in cells c-transfected with miR-141/miR-139 and WT H19. ICAM-1 was confirmed to be targeted by miR-141 and CXCR4 was targeted by miR-139. The H19 expression showed a negative regulatory relationship with the miR-141 and miR-139 expression but a positive regulatory relationship with the ICAM-1 and CXCR4 expression. In summary, the overexpression of H19 in MSC downregulated miR-139 and miR-141, thus increasing the activity of their targets ICAM-1 and CXCR4, respectively, to exhibit therapeutic effects in ulcerative colitis.

Radix Paeoniae Rubra Ameliorates Lupus Nephritis in Lupus-Like Symptoms of Mrl Mice by Reducing Intercellular Cell Adhesion Molecule-1, Vascular Cell Adhesion Molecule-1, and Platelet Endothelial Cell Adhesion Molecule-1 Expression

2020 ◽  
Vol 23 (7) ◽  
pp. 675-683
Author(s):  
Weijie Wang ◽  
Lingyong Cao ◽  
Xinchang Wang ◽  
Yongsheng Fan
Keyword(s):  
Cell Adhesion ◽  
Adhesion Molecule ◽  
Cell Adhesion Molecule ◽  
Treated Group ◽  
Control Group ◽  
Model Group ◽  
Vascular Cell Adhesion ◽  
Platelet Endothelial Cell Adhesion ◽  
Cell Adhesion Molecule 1 ◽  
Intercellular Cell Adhesion Molecule

Objective: Vasculitis is the basic pathological change of systemic lupus erythematosus (SLE). Radix Paeoniae Rubra (RPR), a traditional Chinese herb with the function of reducing blood stasis, has anti-inflammatory and immunoregulatory properties. This study explored the effects of RPR on the kidneys of lupus-like symptoms of mrl (MRL/lpr) mice from the perspective of intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and platelet endothelial cell adhesion molecule-1 (PECAM-1). Methods: Eighteen MRL/lpr lupus model mice were randomly divided into three groups, the model control group, prednisone-treated group, and RPR-treated group, and 6 C57BL/ 6 mice were classified as a control group. After the mice had been treated for 12 weeks, the expression of ICAM-1, VCAM-1 and PECAM-1in the kidney was determined by immunohistochemistry and Reverse Transcription-Polymerase Chain Reaction (RT-PCR). Results: After 12 weeks, there were significant differences in body weight in the model, prednisone and RPR groups compared with the normal group (P <0.05). Pathological observation: Compared with the model group, the proliferation of inflammatory cells infiltrated glomeruli and interstitial cells in prednisone and RPR groups were reduced, and renal pathological damage was reduced. Compared with the model group, urine protein level of prednisone and RPR groups were reduced with no significance (P> 0.05). The mRNA expression levels of ICAM-1 and VCAM-1 were significantly reduced in the prednisone group and RPR group compared with the model group (P <0.05 or P <0.01). Meanwhile, the immunohistochemistry expressions of ICAM-1 and VCAM- 1 expressed in the kidney were significantly reduced in the prednisone group and RPR group (P <0.01 or P <0.05). However, The mRNA expression level and the immunohistochemistry expressions of PECAM-1 expressed in the kidney were reduced in each treatment group (prednisone group and RPR group), but these differences were not significant (P>0.05). Conclusions: ICAM-1, VCAM-1 and PECAM-1 expression in the model group was found to be significantly increased. In addition, RPR could reduce the expression of ICAM-1, VCAM-1 and PECAM-1 in MRL/lpr lupus mice as effectively as prednisone, which may result in the dosage reduction of prednisone, thus decreasing the toxicity and improving the efficacy of prednisone - based treatment of SLE.

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