Highlight on Mouse Endocan

Caires, Nathalie De Freitas; Lassalle, Philippe

doi:10.1161/circresaha.115.306353

Cited by 9 publications

(8 citation statements)

References 10 publications

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“…However, our results show that in mice, Esm-1 inversely correlates with, but does not consistently inhibit, leukocyte infiltration in kidney tissue several weeks after the onset of diabetes. Possible explanations for this observation, include: (1) Esm-1 has some differential functions across species (e.g., due to differential rates of glycosylation) 36 ; (2) constitutive Esm-1 may determine leukocyte infiltration, and we over-expressed Esm-1 in adulthood; (3) Esm-1 may reduce distinct subtypes of macrophages 37 and further leukocyte phenotyping is needed; (4) Esm-1 only alters the amount of resident leukocytes (e.g. macrophages); and/or (5) compensatory mechanisms overcome acute effects of Esm-1, and chronic effects of Esm-1 are on structural features of DKD downstream of infiltrating leukocytes.…”

Section: Discussionmentioning

confidence: 99%

Endothelial Cell-Specific Molecule-1 Inhibits Albuminuria in Diabetic Mice

et al. 2022

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BackgroundDiabetic kidney disease (DKD) is the most common cause of kidney failure in the world, and novel predictive biomarkers and molecular mechanisms of disease are needed. Endothelial cell-specific molecule-1 (Esm-1) is a secreted proteoglycan that attenuates inflammation. We previously identified that a glomerular deficiency of Esm-1 associates with more pronounced albuminuria and glomerular inflammation in DKD-susceptible relative to DKD-resistant mice, but its contribution to DKD remains unexplored.MethodsUsing hydrodynamic tail-vein injection, we overexpress Esm-1 in DKD-susceptible DBA/2 mice and delete Esm-1 in DKD-resistant C57BL/6 mice to study the contribution of Esm-1 to DKD. We analyze clinical indices of DKD, leukocyte infiltration, podocytopenia, and extracellular matrix production. We also study transcriptomic changes to assess potential mechanisms of Esm-1 in glomeruli.ResultsIn DKD-susceptible mice, Esm-1 inversely correlates with albuminuria and glomerular leukocyte infiltration. We show that overexpression of Esm-1 reduces albuminuria and diabetes-induced podocyte injury, independent of changes in leukocyte infiltration. Using a complementary approach, we find that constitutive deletion of Esm-1 in DKD-resistant mice modestly increases the degree of diabetes-induced albuminuria versus wild-type controls. By glomerular RNAseq, we identify that Esm-1 attenuates expression of kidney disease–promoting and interferon (IFN)-related genes, includingAckr2andCxcl11.ConclusionsWe demonstrate that, in DKD-susceptible mice, Esm-1 protects against diabetes-induced albuminuria and podocytopathy, possibly through select IFN signaling. Companion studies in patients with diabetes suggest a role of Esm-1 in human DKD.

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Section: Discussionmentioning

confidence: 99%

Endothelial Cell-Specific Molecule-1 Inhibits Albuminuria in Diabetic Mice

et al. 2022

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“…Indeed, baseline serum endocan could still be detected in BALB/c mice at the time of euthanasia. Moreover, given that mouse endocan can be found in both glycanated and nonglycanated forms (7,35), some of the effects of human endocan could have been antagonized by nonglycanated endocan. Another study in mice lacking endocan should clarify this point.…”

Section: Discussionmentioning

confidence: 99%

Endocan regulates acute lung inflammation through control of leukocyte diapedesis

Gaudet

Portier

Prin

et al. 2019

Journal of Applied Physiology

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Acute respiratory distress syndrome is a severe form of respiratory failure, occurring in up to 20% of patients admitted to the intensive care unit with sepsis. Dysregulated leukocyte diapedesis is a major contributor to acute respiratory distress syndrome. Endocan is a circulating proteoglycan that binds to the leukocyte integrin leukocyte functional antigen-1 and blocks its interaction with its endothelial ligand, ICAM-1. The objective of this study was to evaluate the role of endocan in the control of acute lung inflammation. In vitro, endocan inhibited human leukocyte transendothelial migration as well as ICAM-1-dependent migration but had a very mild effect on ICAM-1-dependent adhesion. Endocan also acted as an inhibitor of transendothelial migration of mouse leukocytes. The effect of systemic administration of recombinant human endocan was assessed in a model of acute lung inflammation in BALB/c mice. Treatment with endocan 1 h after intratracheal LPS challenge reduced the alveolar inflammatory response, diminished histological features of acute lung injury, and improved respiratory function. These results highlight the anti-inflammatory role of human endocan and its protective effect against acute lung injury. NEW & NOTEWORTHY We show here that endocan inhibits ICAM-1-dependent human leukocyte transendothelial migration and ICAM-1-dependent adhesion. We also found that in BALB/c mice with tracheal LPS-induced acute lung injury treatment with recombinant human endocan reduces lung inflammation, notably through reduction of neutrophilic recruitment, and restores normal lung function. These results confirm the hypothesis that human endocan may have a protective effect against acute lung inflammation.

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“…1; Supplementary Table S2a), which was not the case with mouse TNBC cell line 4T1/luc2 (Supplementary Table S2b). In fact, mouse endocan is less glycanated than human endocan, and its biological properties are completely opposite to human endocan [26, 27]. Unlike MDA-MB-231SCP2, some other metastatic human TNBC cell lines were reported to overexpress ESM1 [28]; however, no proliferation rates were available for those cell lines.…”

Section: Discussionmentioning

confidence: 99%

Endocan as a prognostic biomarker of triple-negative breast cancer

Sagara

Igarashi

Otsuka

et al. 2016

Breast Cancer Res Treat

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PurposeTriple-negative breast cancer (TNBC) has aggressive characteristics and fewer treatment options than other subtypes. The purpose of this study was to explore prognostic biomarkers for TNBC that can be easily detected from the blood samples.MethodsMDA-MB-231 and MDA-MB-231BR, a brain metastatic variant of the human TNBC cell line MDA-MB-231, were used as less and more aggressive models of TNBC, respectively. The extent to which the candidate gene/protein identified by RNA sequencing correlated well with aggressiveness of TNBC and how much protein was detected from the blood of tumor-bearing mice were evaluated.ResultsBoth the in vitro proliferation and in vivo tumor growth of MDA-MB-231BR were more rapid than those of MDA-MB-231. RNA sequencing identified ESM1 as a gene that was expressed significantly more in MDA-MB-231BR than in MDA-MB-231, and qRT-PCR confirmed a significantly higher expression of ESM1 in MDA-MB-231BR xenograft in vivo. Furthermore, Kaplan–Meier analysis of relapse-free survival demonstrated that TNBC patients with high ESM1 expression had clearly worse relapse-free survival than those with low ESM1 expression, which was consistent with our preclinical findings. Endocan, a protein of ESM1 gene product, was successfully detected in both conditioned medium from MDA-MB-231BR and plasma samples from mice bearing MDA-MB-231BR xenograft, which showed a significantly distinct pattern from less aggressive MDA-MB-231. Moreover, bisulfite sequence analysis revealed that overexpression of ESM1 in MDA-MB-231BR might be attributed to DNA demethylation in an upstream region of the ESM1 gene.ConclusionThis study indicates that endocan could be used as a blood-based prognostic biomarker in TNBC patients.Electronic supplementary materialThe online version of this article (doi:10.1007/s10549-016-4057-8) contains supplementary material, which is available to authorized users.

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Highlight on Mouse Endocan

Cited by 9 publications

References 10 publications

Endothelial Cell-Specific Molecule-1 Inhibits Albuminuria in Diabetic Mice

Endothelial Cell-Specific Molecule-1 Inhibits Albuminuria in Diabetic Mice

Endocan regulates acute lung inflammation through control of leukocyte diapedesis

Endocan as a prognostic biomarker of triple-negative breast cancer

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