Role of Rho GTPases in thrombin-induced lung vascular endothelial cells barrier dysfunction

Birukova, Anna A.; Smurova, K. M.; Birukov, Konstantin G.; Kaibuchi, Kozo; Garcia, Joe G.N.; Verin, Alexander D.

doi:10.1016/j.mvr.2003.09.007

Cited by 251 publications

(299 citation statements)

References 56 publications

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“…Rac and Rap activation assays were performed using commercially available assay kits purchased from Upstate Biotechnology (Lake Placid, NY), as previously described [12,13]. In brief, cells were treated with vehicle or stimulated with PGE 2 or beraprost for various periods of time.…”

Section: Measurements Of Camp or Cgmp Accumulationmentioning

confidence: 99%

“…The cellular barrier properties were analyzed by measurements of transendothelial electrical resistance (TER) across confluent human pulmonary artery endothelial monolayers using an electrical cell-substrate impedance sensing system (Applied Biophysics, Troy, NY) as previously described [12,13,40].…”

Section: Measurement Of Transendothelial Electrical Resistancementioning

confidence: 99%

“…Endothelial cells plated on glass coverslips were grown to confluence, stimulated with PGs or left untreated, and immunofluorescent staining of proteins of interest using corresponding antibodies was performed as described elsewhere [12,13,43]. Images were processed with Adobe Photoshop 7.0 (Adobe Systems, San Jose, CA) software.…”

Section: Immunofluorescent Stainingmentioning

confidence: 99%

“…Immunoblotting detection of proteins of interest was performed as described previously [12,43]. In brief, protein extracts were subjected to 12.5% or 7.5% SDS-PAGE, transferred to nitrocellulose membrane in semidry transfer apparatus (BioRad, Hercules, CA) 10 V for 1 hour, and probed with antibody of interest.…”

Section: Western Blot Analysismentioning

confidence: 99%

“…In addition, both barrier-protective and barrier-disruptive processes in EC are differentially regulated by small GTPases Rac and Rho, which induce distinct patterns of cytoskeletal and cell contact remodeling leading to EC barrier protection or compromise [9][10][11][12][13].…”

Section: Introductionmentioning

confidence: 99%

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Prostaglandins PGE2 and PGI2 promote endothelial barrier enhancement via PKA- and Epac1/Rap1-dependent Rac activation

Birukova

Zagranichnaya

et al. 2007

Experimental Cell Research

261

267

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Prostaglandin E 2 (PGE 2 ) and prostacyclin are lipid mediators produced by cyclooxygenase and implicated in the regulation of vascular function, wound repair, inflammatory processes, and acute lung injury. Although protective effects of these prostaglandins (PGs) are associated with stimulation of intracellular cAMP production, the crosstalk between cAMP-activated signal pathways in the regulation of endothelial cell (EC) permeability is not well understood. We studied involvement of cAMP-dependent kinase (PKA), cAMP-Epac-Rap1 pathway, and small GTPase Rac in the PGsinduced EC barrier protective effects and cytoskeletal remodeling. PGE 2 and PGI 2 synthetic analog beraprost increased transendothelial electrical resistance and decreased dextran permeability, enhanced peripheral F-actin rim and increased intercellular adherens junction areas reflecting EC barrier-protective response. Furthermore, beraprost dramatically attenuated thrombin-induced Rho activation, MLC phosphorylation and EC barrier dysfunction. In vivo, beraprost attenuated lung barrier dysfunction induced by high tidal volume mechanical ventilation. Both PGs caused cAMPmediated activation of PKA-, Epac/Rap1-and Tiam1/Vav2-dependent pathways of Rac1 activation and EC barrier regulation. Knockdown of Epac, Rap1, Rac-specific exchange factors Tiam1 and Vav2 using siRNA approach, or inhibition of PKA activity decreased Rac1 activation and PGinduced EC barrier enhancement. Thus, our results show that barrier-protective effects of PGE 2 and prostacyclin on pulmonary EC are mediated by PKA and Epac/Rap pathways, which converge on Rac activation and lead to enhancement of peripheral actin cytoskeleton and adherens junctions. These mechanisms may mediate protective effects of PGs against agonist-induced lung vascular barrier dysfunction in vitro and against mechanical stress-induced lung injury in vivo.

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Section: Measurements Of Camp or Cgmp Accumulationmentioning

confidence: 99%

Section: Measurement Of Transendothelial Electrical Resistancementioning

confidence: 99%

Section: Immunofluorescent Stainingmentioning

confidence: 99%

Section: Western Blot Analysismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Prostaglandins PGE2 and PGI2 promote endothelial barrier enhancement via PKA- and Epac1/Rap1-dependent Rac activation

Birukova

Zagranichnaya

et al. 2007

Experimental Cell Research

261

267

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MYPT1 inhibits the metastasis of renal clear cell carcinoma via the MAPK8/N‐cadherin pathway

et al. 2022

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Myosin phosphatase target subunit 1 (MYPT1) is a subunit of myosin phosphatase that is capable of regulating smooth muscle contraction. MYPT1 has been reported to be involved in a wide variety of tumours, but its expression and biological functions in renal clear cell carcinoma (ccRCC) remain obscure. Herein, we analysed the relationship between patient clinicopathological characteristics and MYPT1 expression levels in ccRCC patients using a tissue microarray (TMA) and data retrieved from the TCGA‐KIRC dataset. MYPT1 was overexpressed or depleted using siRNA in ccRCC cells to assess the effects on migration and invasion in vitro and in vivo. Additionally, RNA‐sequencing and bioinformatics analysis were performed to investigate the precise mechanism. MYPT1 expression in ccRCC tissues was observed to be lower than that in nonmalignant tissues (P < 0.05). In addition, MYPT1 downregulation was closely linked to advanced pathological stage (P < 0.05), and poor OS (overall survival; P < 0.05). Functionally, increased expression of MYPT1 suppressed ccRCC migration and invasion in vitro, and inhibited tumour metastasis in vivo. In addition, MYPT1 overexpression exerted its suppressive effects via the MAPK8/N‐cadherin pathway in ccRCC.

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Signaling To and Through The Endothelial Adherens Junction

Ferreri

Vincent

2008

Cell Junctions

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Role of Rho GTPases in thrombin-induced lung vascular endothelial cells barrier dysfunction

Cited by 251 publications

References 56 publications

Prostaglandins PGE2 and PGI2 promote endothelial barrier enhancement via PKA- and Epac1/Rap1-dependent Rac activation

Prostaglandins PGE2 and PGI2 promote endothelial barrier enhancement via PKA- and Epac1/Rap1-dependent Rac activation

MYPT1 inhibits the metastasis of renal clear cell carcinoma via the MAPK8/N‐cadherin pathway

Signaling To and Through The Endothelial Adherens Junction

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