Fibrinogen Protects Against Barrier Dysfunction Through Maintaining Cell Surface Syndecan-1 In Vitro

Wu, Feng; Kozar, Rosemary A.

doi:10.1097/shk.0000000000001207

Cited by 31 publications

(45 citation statements)

References 31 publications

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“…The precise mechanism by which syndecan contributes to barrier integrity has not been well-elucidated. Our recent data demonstrated that fibrinogen (a major protein in blood) binding to sydnecan-1 on the endothelial cell surface activates the PAK1/cofilin intra-cellular signaling pathway to maintain endothelial barrier integrity 13,14 . However, much less is known about the regulation of Sdc1 expression, representing a gap in our knowledge.…”

Section: Our Results Demonstrate That Mir-19b Was Increased In Hemorrmentioning

confidence: 99%

“…Primary endothelial cell culture. Human lung microvascular endothelial cells (HLMEC; Lonza, MD) were cultured as we described previously 13 . miR-19b mimic and miR-19b inhibitor transfection.…”

Section: Methodsmentioning

confidence: 99%

“…Human lung microvascular endothelial cells (HLMEC; Lonza, MD) were cultured as we described previously 13 .…”

Section: Methodsmentioning

confidence: 99%

“…Some monolayers were transfected with 100 nM miR-19b mimics, scRNA, miR-19b oligo inhibitors, or neRNA and subjected to normoxia and H/R as described above. FITC-dextran transwell permeability assay and stress fiber staining were performed as we described previously 13 .…”

Section: Hypoxia/reoxygenation (H/rmentioning

confidence: 99%

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miR-19b targets pulmonary endothelial syndecan-1 following hemorrhagic shock

Wang

Chao

et al. 2020

Sci Rep

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Hemorrhagic shock results in systemic injury to the endothelium contributing to post-shock morbidity and mortality. The mechanism involves syndecan-1, the backbone of the endothelial glycocalyx. We have shown in a rodent model that lung syndecan-1 mRNA is reduced following hemorrhage, whereas the molecular mechanism underlying the mRNA reduction is not clear. In this study, we present evidence that miR-19b targets syndecan-1 mRNA to downregulate its expression. Our results demonstrate that miR-19b was increased in hemorrhagic shock patients and in-vitro specifically bound to syndecan-1 mRNA and caused its degradation. Further, hypoxia/reoxygenation (H/R), our in vitro hemorrhage model, increased miR-19b expression in human lung microvascular endothelial cells, leading to a decrease in syndecan-1 mRNA and protein. H/R insult and miR-19b mimic overexpression comparably exaggerated permeability and enhanced endothelial barrier breakdown. The detrimental role of miR-19b in inducing endothelial dysfunction was confirmed in vivo. Lungs from mice undergoing hemorrhagic shock exhibited a significant increase in miR-19b and a concomitant decrease in syndecan-1 mRNA. Pretreatment with miR-19b oligo inhibitor significantly decreased lung injury, inflammation, and permeability and improved hemodynamics. These findings suggest that inhibition of miR-19b may be a putative therapeutic avenue for mitigating post shock pulmonary endothelial dysfunction in hemorrhage shock.

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Section: Our Results Demonstrate That Mir-19b Was Increased In Hemorrmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

“…Human lung microvascular endothelial cells (HLMEC; Lonza, MD) were cultured as we described previously 13 .…”

Section: Methodsmentioning

confidence: 99%

Section: Hypoxia/reoxygenation (H/rmentioning

confidence: 99%

See 2 more Smart Citations

miR-19b targets pulmonary endothelial syndecan-1 following hemorrhagic shock

Wang

Chao

et al. 2020

Sci Rep

Self Cite

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show abstract

“…fibrinogen, which is critically depleted first during bleeding [8]), TXA, and permissive hypotension along with surgical bleeding control to limit further blood loss and stabilize coagulation function pre-hospital may be an alternative as outlined in the updated European trauma guideline [9]. Protective effects to the glycocalyx and endothelial barrier integrity have been linked to the fibrinogen component rather than to plasma per se [10]. A median 3.8 g fibrinogen concentrate can increase clot stability by 5.2 mm at 5 min of viscoelastic test initiation while TXA can decrease lysis by 5.4% [11].…”

mentioning

confidence: 99%