scholarly journals Keratinocyte growth factor reduces alveolar epithelial susceptibility to in vitro mechanical deformation

2001 ◽  
Vol 281 (5) ◽  
pp. L1068-L1077 ◽  
Author(s):  
Jane Oswari ◽  
Michael A. Matthay ◽  
Susan S. Margulies
Keyword(s):  
Cell Death ◽  
Growth Factor ◽  
Lung Injury ◽  
Keratinocyte Growth Factor ◽  
Alveolar Type ◽  
Alveolar Epithelial ◽  
Ventilator Induced Lung Injury ◽  
And Control

Keratinocyte growth factor (KGF) is a potent mitogen that prevents lung epithelial injury in vivo. We hypothesized that KGF treatment reduces ventilator-induced lung injury by increasing the alveolar epithelial tolerance to mechanical strain. We evaluated the effects of in vivo KGF treatment to rats on the response of alveolar type II (ATII) cells to in vitro controlled, uniform deformation. KGF (5 mg/kg) or saline (no-treatment control) was instilled intratracheally in rats, and ATII cells were isolated 48 h later. After 24 h in culture, both cell groups were exposed to 1 h of continuous cyclic strain (25% change in surface area); undeformed wells were included as controls. Cytotoxicity was evaluated quantitatively with fluorescent immunocytochemistry. There was >1% cell death in undeformed KGF-treated and control groups. KGF pretreatment significantly reduced deformation-related cell mortality to only 2.2 ± 1.3% (SD) from 49 ± 5.5% in control wells ( P < 0.001). Effects of extracellular matrix, actin cytoskeleton, and phenotype of KGF-treated and control cells were examined. The large reduction in deformation-induced cell death demonstrates that KGF protects ATII cells by increasing their strain tolerance and supports KGF treatment as a potential preventative measure for ventilator-induced lung injury.

Mo1922 Keratinocyte Growth Factor Protects Against C. difficile Toxin-Induced Injury, Cell Death and Apopotisis In Vitro and In Vivo

2016 ◽  
Vol 150 (4) ◽  
pp. S816-S817
Author(s):  
Jason Bau ◽  
Basmah Alhassan ◽  
Jordan Roth ◽  
Jimmie Nguyen ◽  
Xander Harris ◽  
...  
Keyword(s):  
Cell Death ◽  
Growth Factor ◽  
Keratinocyte Growth Factor

Keratinocyte growth factor can enhance alveolar epithelial repair by nonmitogenic mechanisms

2002 ◽  
Vol 283 (1) ◽  
pp. L163-L169 ◽  
Author(s):  
Kamran Atabai ◽  
Masanobu Ishigaki ◽  
Thomas Geiser ◽  
Iris Ueki ◽  
Michael A. Matthay ◽  
...  
Keyword(s):  
Growth Factor ◽  
Egf Receptor ◽  
Keratinocyte Growth Factor ◽  
Alveolar Epithelial Cells ◽  
Type Ii ◽  
Epithelial Repair ◽  
Alveolar Epithelial ◽  
And Migration

Pretreatment with keratinocyte growth factor (KGF) ameliorates experimentally induced acute lung injury in rats. Although alveolar epithelial type II cell hyperplasia probably contributes, the mechanisms underlying KGF's protective effect remain incompletely described. Therefore, we tested the hypothesis that KGF given to rats in vivo would enhance alveolar epithelial repair in vitro by nonproliferative mechanisms. After intratracheal instillation (48 h) of KGF (5 mg/kg), alveolar epithelial type II cells were isolated for in vitro alveolar epithelial repair studies. KGF-treated cells had markedly increased epithelial repair (96 ± 22%) compared with control cells ( P < 0.001). KGF-treated cells had increased cell spreading and migration at the wound edge but no increase in in vitro proliferation compared with control cells. KGF-treated cells were more adherent to extracellular matrix proteins and polystyrene. Inhibition of the epidermal growth factor (EGF) receptor with tyrosine kinase inhibitors abolished the KGF effect on epithelial repair. In conclusion, in vivo administration of KGF augments the epithelial repair rate of alveolar epithelial cells by altering cell adherence, spreading, and migration and through stimulation of the EGF receptor.

Gene transfer of hepatocyte growth factor by electroporation reduces bleomycin-induced lung fibrosis

2007 ◽  
Vol 292 (2) ◽  
pp. L529-L536 ◽  
Author(s):  
Amiq Gazdhar ◽  
Patrick Fachinger ◽  
Coretta van Leer ◽  
Jaroslaw Pierog ◽  
Mathias Gugger ◽  
...  
Keyword(s):  
Growth Factor ◽  
Gene Transfer ◽  
Pulmonary Fibrosis ◽  
Wound Repair ◽  
Alveolar Epithelial Cells ◽  
Epithelial Repair ◽  
Alveolar Epithelial ◽  
Hepatocyte Growth

Abnormal alveolar wound repair contributes to the development of pulmonary fibrosis after lung injury. Hepatocyte growth factor (HGF) is a potent mitogenic factor for alveolar epithelial cells and may therefore improve alveolar epithelial repair in vitro and in vivo. We hypothesized that HGF could increase alveolar epithelial repair in vitro and improve pulmonary fibrosis in vivo. Alveolar wound repair in vitro was determined using an epithelial wound repair model with HGF-transfected A549 alveolar epithelial cells. Electroporation-mediated, nonviral gene transfer of HGF in vivo was performed 7 days after bleomycin-induced lung injury in the rat. Alveolar epithelial repair in vitro was increased after transfection of wounded epithelial monolayers with a plasmid encoding human HGF, pCikhHGF [human HGF (hHGF) gene expressed from the cytomegalovirus (CMV) immediate-early promoter and enhancer] compared with medium control. Electroporation-mediated in vivo HGF gene transfer using pCikhHGF 7 days after intratracheal bleomycin reduced pulmonary fibrosis as assessed by histology and hydroxyproline determination 14 days after bleomycin compared with controls treated with the same vector not containing the HGF sequence (pCik). Lung epithelial cell proliferation was increased and apoptosis reduced in hHGF-treated lungs compared with controls, suggesting increased alveolar epithelial repair in vivo. In addition, profibrotic transforming growth factor-β1 (TGF-β1) was decreased in hHGF-treated lungs, indicating an involvement of TGF-β1 in hHGF-induced reduction of lung fibrosis. In conclusion, electroporation-mediated gene transfer of hHGF decreases bleomycin-induced pulmonary fibrosis, possibly by increasing alveolar epithelial cell proliferation and reducing apoptosis, resulting in improved alveolar wound repair.

scholarly journals A Novel Solid-Phase Site-Specific PEGylation Enhances the In Vitro and In Vivo Biostabilty of Recombinant Human Keratinocyte Growth Factor 1

PLoS ONE ◽  
2012 ◽  
Vol 7 (5) ◽  
pp. e36423 ◽  
Author(s):  
Zhifeng Huang ◽  
Guanghui Zhu ◽  
Chuanchuan Sun ◽  
Jingui Zhang ◽  
Yi Zhang ◽  
...  
Keyword(s):  
Growth Factor ◽  
Solid Phase ◽  
Keratinocyte Growth Factor ◽  
Site Specific ◽  
Human Keratinocyte

scholarly journals Bcl-2 overexpression in type II epithelial cells does not prevent hyperoxia-induced acute lung injury in mice

2010 ◽  
Vol 299 (3) ◽  
pp. L312-L322 ◽  
Author(s):  
Isabelle Métrailler-Ruchonnet ◽  
Alessandra Pagano ◽  
Stéphanie Carnesecchi ◽  
Karim Khatib ◽  
Pedro Herrera ◽  
...  
Keyword(s):  
Cell Death ◽  
Epithelial Cells ◽  
Lung Injury ◽  
Ex Vivo ◽  
Lung Damage ◽  
Type Ii Cells ◽  
Type Ii ◽  
Lung Weight

Bcl-2 is an anti-apoptotic molecule preventing oxidative stress damage and cell death. We have previously shown that Bcl-2 is able to prevent hyperoxia-induced cell death when overexpressed in a murine fibrosarcoma cell line L929. We hypothesized that its specific overexpression in pulmonary epithelial type II cells could prevent hyperoxia-induced lung injury by protecting the epithelial side of the alveolo-capillary barrier. In the present work, we first showed that in vitro Bcl-2 can rescue murine pulmonary epithelial cells (MLE12) from oxygen-induced cell apoptosis, as shown by analysis of LDH release, annexin V/propidium staining, and caspase-3 activity. We then generated transgenic mice overexpressing specifically Bcl-2 in lung epithelial type II cells under surfactant protein C (SP-C) promoter (Tg-Bcl-2) and exposed them to hyperoxia. Bcl-2 did not hinder hyperoxia-induced mitochondria and DNA oxidative damage of type II cell in vivo. Accordingly, lung damage was identical in both Tg-Bcl-2 and littermate mice strains, as measured by lung weight, bronchoalveolar lavage, and protein content. Nevertheless, we observed a significant lower number of TUNEL-positive cells in type II cells isolated from Tg-Bcl-2 mice exposed to hyperoxia compared with cells isolated from littermate mice. In summary, these results show that although Bcl-2 overexpression is able to prevent hyperoxia-induced cell death at single cell level in vitro and ex vivo, it is not sufficient to prevent cell death of parenchymal cells and to protect the lung from acute damage in mice.

scholarly journals Ventilator-induced lung-injury in mouse models: Is there a trap?

2021 ◽  
Vol 37 (1) ◽  
Author(s):  
Jon Petur Joelsson ◽  
Saevar Ingthorsson ◽  
Jennifer Kricker ◽  
Thorarinn Gudjonsson ◽  
Sigurbergur Karason
Keyword(s):  
Mechanical Ventilation ◽  
Lung Injury ◽  
Mouse Models ◽  
Mechanical Strain ◽  
Acute Injury ◽  
In Vivo Studies ◽  
Cellular Interactions ◽  
Ventilator Induced Lung Injury

AbstractVentilator-induced lung injury (VILI) is a serious acute injury to the lung tissue that can develop during mechanical ventilation of patients. Due to the mechanical strain of ventilation, damage can occur in the bronchiolar and alveolar epithelium resulting in a cascade of events that may be fatal to the patients. Patients requiring mechanical ventilation are often critically ill, which limits the possibility of obtaining patient samples, making VILI research challenging. In vitro models are very important for VILI research, but the complexity of the cellular interactions in multi-organ animals, necessitates in vivo studies where the mouse model is a common choice. However, the settings and duration of ventilation used to create VILI in mice vary greatly, causing uncertainty in interpretation and comparison of results. This review examines approaches to induce VILI in mouse models for the last 10 years, to our best knowledge, summarizing methods and key parameters presented across the studies. The results imply that a more standardized approach is warranted.

Flaxseed Lignans Protect Against Acid Aspiration‐Induced Acute Lung Injury In Vivo and H 2 O 2 ‐Induced Cell Death In Vitro

2007 ◽  
Vol 21 (5) ◽  
Author(s):  
James C Lee ◽  
Evguenia Arguiri ◽  
C. C. Solomides ◽  
Melpo Christofidou Solomidou
Keyword(s):  
Cell Death ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Acid Aspiration ◽  
Flaxseed Lignans
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