Peptide XIB13 reduces capillary leak in a rodent burn model

Goertz, Ole; Lauer, Henrik; Lohe, Leon von der; Lehnhardt, Marcus; Schossleitner, Klaudia; Petzelbauer, Max; Petzelbauer, Peter

doi:10.1016/j.mvr.2014.04.003

Cited by 8 publications

(14 citation statements)

References 26 publications

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“…Evidence supporting a role of cingulin in the regulation of barrier function of endothelial cells also comes from studies showing that a peptide based on the N-terminal sequence of cingulin increases barrier function and reduces edema formation in an animal burn model 39 and in a lung transplantation model. 40 This is directly shown in our CGN −/− mice.…”

Section: Discussionmentioning

confidence: 99%

Evidence That Cingulin Regulates Endothelial Barrier Function In Vitro and In Vivo

Schossleitner

Rauscher

Gröger

et al. 2016

ATVB

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Objective-Cingulin is a cytoplasmic component of tight junctions. Although modulation of cingulin levels in cultured epithelial model systems has no significant effect on barrier function, evidence from cingulin knockout mice suggests that cingulin may be involved in the regulation of the behavior of epithelial or endothelial cells. Here, we investigate the role of cingulin in the barrier function of endothelial cells. Approach and Results-We show that cingulin is expressed in human endothelial cells of the skin, brain, and lung in vivo and in vitro. Endothelial cingulin colocalizes and coimmunoprecipitates with the tight junction proteins zonula occludens-1 and guanine nucleotide exchange factor-H1. Cingulin overexpression in human umbilical vein endothelial cell induces tight junction formation, increases transendothelial electric resistance, and strengthens barrier function for low and high molecular weight tracers. In contrast, cultured endothelial cells lacking cingulin are more permeable for low molecular weight tracers. In cingulin knockout mice, neurons of the area postrema and Purkinje cells show an increased uptake of small molecular weight tracers indicating decreased barrier function at these sites. The expression of cingulin in endothelial cells has been poorly characterized because early studies showed a low abundance of cingulin in endothelial cells when compared with epithelia. 18,19 However, the recently characterized role of GEF-H1 in regulating endothelial permeability 20,21 raises the possibility that cingulin is a key regulator of endothelial barrier function. Conclusions-WeHere, we studied the expression and molecular environment of cingulin in different types of endothelial cells. Furthermore, we characterized the effects of exogenous cingulin expression or deletion of the cingulin head domain on the expression of claudin-5 and endothelial barrier function and analyzed barrier function in cingulin-deficient mice. The results indicate that expression levels of cingulin contribute to regulating endothelial barrier function. Materials and MethodsMaterials and Methods are available in the online-only Data Supplement. Results Cingulin Is Localized at Human Endothelial TJ In SituWe analyzed the expression of cingulin in different vascular beds by immunohistochemistry. Endothelial cells of large and small-sized veins and arteries in human skin, lung, and brain tissues stained positive with anticingulin antibodies ( Figure 1A). By immunofluorescence, cingulin labeling was detected in close proximity of VE-cadherin labeling with a Pearson correlation coefficient of 0.11, but was colocalizing with ZO-1 labeling resulting in a Pearson correlation coefficient of 0.31 ( Figure 1B), supporting the notion that cingulin is associated with TJ of endothelial cells. 22 Analysis of mRNA expression levels of cingulin relative to VE-cadherin in different tissues and vessels showed that cingulin expression was detectable in the brain, the vena cava, and the aorta, whereas no expression was detected in muscle an...

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Section: Discussionmentioning

confidence: 99%

Evidence That Cingulin Regulates Endothelial Barrier Function In Vitro and In Vivo

Schossleitner

Rauscher

Gröger

et al. 2016

ATVB

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“…Several treatment modalities to improve blood flow by thrombolysis and vasodilatation or to reduce edema were tested. However, the majority of research studies has not been followed up or was performed without adequate controls [1,[12][13][14][15].…”

Section: Introductionmentioning

confidence: 99%

Influence of ISDN, l-NAME and selenium on microcirculation, leukocyte endothelium interaction and angiogenesis after frostbite

Goertz¹,

Haddad²,

Lohe³

et al. 2015

Burns

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“…The red blood cell velocity (mm/s) was calculated by the computer program CapImage 1 (CapImage 1 , Dr. Zeintl, Heidelberg, Germany). To assess edema formation, the plasma marker FITC-dextran was used [13]. Its extravasation leads to different fluorensce intensities intraand extravassaly, the ratio of which was used to express edema formation.…”

Section: Measurementsmentioning

confidence: 99%

“…The utilized model allows for reliable in vivo assessment of microcirculatory parameters over the course of healing after thermal injury [2, [13][14][15][16][17][18]. The deep thickness depth of these burns was verified by histological samples in the past [2,16].…”

Section: Burn Modelmentioning

confidence: 99%

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Prednisolone but not selenium and rtPA reduces edema and improves angiogenesis after burn in mice

Goertz

Över

Lohe

et al. 2016

Burns

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Peptide XIB13 reduces capillary leak in a rodent burn model

Cited by 8 publications

References 26 publications

Evidence That Cingulin Regulates Endothelial Barrier Function In Vitro and In Vivo

Evidence That Cingulin Regulates Endothelial Barrier Function In Vitro and In Vivo

Influence of ISDN, l-NAME and selenium on microcirculation, leukocyte endothelium interaction and angiogenesis after frostbite

Prednisolone but not selenium and rtPA reduces edema and improves angiogenesis after burn in mice

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