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Asef controls vascular endothelial permeability and barrier recovery in the lung.

Tian X, Tian Y, Gawlak G, Meng F, Kawasaki Y, Akiyama T, Birukova AA - Mol. Biol. Cell (2014)

Bottom Line: Molecular inhibition of Asef attenuated HGF-induced peripheral accumulation of cortactin, formation of lamellipodia-like structures, and enhancement of VE-cadherin adherens junctions and compromised HGF-protective effect against thrombin-induced RhoA GTPase activation, Rho-dependent cytoskeleton remodeling, and EC permeability.This effect was lost in Asef(-/-) mice.This study shows for the first time the role of Asef in HGF-mediated protection against endothelial hyperpermeability and lung injury.

View Article: PubMed Central - PubMed

Affiliation: Section of Pulmonary and Critical Care Medicine, Department of Medicine, University of Chicago, Chicago, IL 60637.

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Role of Asef in the HGF protection against leukocyte infiltration in TRAP6/HTV-induced lung injury. Asef+/+ and Asef−/− mice were treated with vehicle or HGF (500 μg/kg, intravenous), followed by TRAP6 injection (1.5 × 10−5 mol/kg, intratracheal) and mechanical ventilation at high tidal volume (HTV, 30 ml/kg, 4 h). (A) Total cell count and neutrophil count were performed in BAL fluid; n = 6. (B) Measurements of MPO activity in lung samples from Asef+/+ and Asef−/− mice exposed to TRAP6/HTV with or without HGF pretreatment; n = 4. (C) Whole lungs were fixed in 10% Formalin and used for histological evaluation by hematoxylin and eosin staining. Images are representative of four to six lung specimens for each condition with 40× magnification. Insets, higher-magnification images of lung tissue.
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Figure 9: Role of Asef in the HGF protection against leukocyte infiltration in TRAP6/HTV-induced lung injury. Asef+/+ and Asef−/− mice were treated with vehicle or HGF (500 μg/kg, intravenous), followed by TRAP6 injection (1.5 × 10−5 mol/kg, intratracheal) and mechanical ventilation at high tidal volume (HTV, 30 ml/kg, 4 h). (A) Total cell count and neutrophil count were performed in BAL fluid; n = 6. (B) Measurements of MPO activity in lung samples from Asef+/+ and Asef−/− mice exposed to TRAP6/HTV with or without HGF pretreatment; n = 4. (C) Whole lungs were fixed in 10% Formalin and used for histological evaluation by hematoxylin and eosin staining. Images are representative of four to six lung specimens for each condition with 40× magnification. Insets, higher-magnification images of lung tissue.

Mentions: Exposure to TRAP6/HTV also significantly increased the total cell and neutrophil count in BAL samples in both Asef+/+ and Asef−/− mice as compared with the nonventilated controls (Figure 9A). Although we observed a trend toward higher levels of BAL cell count in TRAP6/HTV-treated Asef−/− mice, it did not reach statistical significance. By contrast, HGF administration before TRAP6/HTV caused significant reduction of cellular infiltration in Asef+/+ but not Asef−/− mice. TRAP6/HTV caused a significant increase in lung myeloperoxidase (MPO) activity compared with the control group (Figure 9B). HGF decreased MPO activity in the lungs of TRAP6/HTV-exposed Asef+/+ mice, whereas in Asef−/− mice, this effect was statistically insignificant.


Asef controls vascular endothelial permeability and barrier recovery in the lung.

Tian X, Tian Y, Gawlak G, Meng F, Kawasaki Y, Akiyama T, Birukova AA - Mol. Biol. Cell (2014)

Role of Asef in the HGF protection against leukocyte infiltration in TRAP6/HTV-induced lung injury. Asef+/+ and Asef−/− mice were treated with vehicle or HGF (500 μg/kg, intravenous), followed by TRAP6 injection (1.5 × 10−5 mol/kg, intratracheal) and mechanical ventilation at high tidal volume (HTV, 30 ml/kg, 4 h). (A) Total cell count and neutrophil count were performed in BAL fluid; n = 6. (B) Measurements of MPO activity in lung samples from Asef+/+ and Asef−/− mice exposed to TRAP6/HTV with or without HGF pretreatment; n = 4. (C) Whole lungs were fixed in 10% Formalin and used for histological evaluation by hematoxylin and eosin staining. Images are representative of four to six lung specimens for each condition with 40× magnification. Insets, higher-magnification images of lung tissue.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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Figure 9: Role of Asef in the HGF protection against leukocyte infiltration in TRAP6/HTV-induced lung injury. Asef+/+ and Asef−/− mice were treated with vehicle or HGF (500 μg/kg, intravenous), followed by TRAP6 injection (1.5 × 10−5 mol/kg, intratracheal) and mechanical ventilation at high tidal volume (HTV, 30 ml/kg, 4 h). (A) Total cell count and neutrophil count were performed in BAL fluid; n = 6. (B) Measurements of MPO activity in lung samples from Asef+/+ and Asef−/− mice exposed to TRAP6/HTV with or without HGF pretreatment; n = 4. (C) Whole lungs were fixed in 10% Formalin and used for histological evaluation by hematoxylin and eosin staining. Images are representative of four to six lung specimens for each condition with 40× magnification. Insets, higher-magnification images of lung tissue.
Mentions: Exposure to TRAP6/HTV also significantly increased the total cell and neutrophil count in BAL samples in both Asef+/+ and Asef−/− mice as compared with the nonventilated controls (Figure 9A). Although we observed a trend toward higher levels of BAL cell count in TRAP6/HTV-treated Asef−/− mice, it did not reach statistical significance. By contrast, HGF administration before TRAP6/HTV caused significant reduction of cellular infiltration in Asef+/+ but not Asef−/− mice. TRAP6/HTV caused a significant increase in lung myeloperoxidase (MPO) activity compared with the control group (Figure 9B). HGF decreased MPO activity in the lungs of TRAP6/HTV-exposed Asef+/+ mice, whereas in Asef−/− mice, this effect was statistically insignificant.

Bottom Line: Molecular inhibition of Asef attenuated HGF-induced peripheral accumulation of cortactin, formation of lamellipodia-like structures, and enhancement of VE-cadherin adherens junctions and compromised HGF-protective effect against thrombin-induced RhoA GTPase activation, Rho-dependent cytoskeleton remodeling, and EC permeability.This effect was lost in Asef(-/-) mice.This study shows for the first time the role of Asef in HGF-mediated protection against endothelial hyperpermeability and lung injury.

View Article: PubMed Central - PubMed

Affiliation: Section of Pulmonary and Critical Care Medicine, Department of Medicine, University of Chicago, Chicago, IL 60637.

Show MeSH
Related in: MedlinePlus