scholarly journals 490. Electroporation-Mediated Gene Transfer of Caveolin-1 Protects from Bleomycin-Induced Pulmonary Fibrosis Through Regulating Activation of Inflammasome

2016 ◽  
Vol 24 ◽  
pp. S194
Author(s):  
Xin Lin ◽  
Michael Barravecchia ◽  
David A Dean
Keyword(s):  
Gene Transfer ◽  
Pulmonary Fibrosis ◽  
Caveolin 1

scholarly journals Caveolin-1 gene therapy inhibits inflammasome activation to protect from bleomycin-induced pulmonary fibrosis

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Xin Lin ◽  
Michael Barravecchia ◽  
R. Matthew Kottmann ◽  
Patricia Sime ◽  
David A Dean
Keyword(s):  
Gene Transfer ◽  
Pulmonary Fibrosis ◽  
Inflammasome Activation ◽  
Type I ◽  
Caveolin 1 ◽  
Alveolar Epithelial ◽  
Caspase 1 ◽  
I Cells ◽  
Mouse Lungs ◽  
Inflammasome Activity

AbstractIdiopathic pulmonary fibrosis (IPF) is a devastating and fatal disease and characterized by increased deposition of extracellular matrix proteins and scar formation in the lung, resulting from alveolar epithelial damage and accumulation of inflammatory cells. Evidence suggests that Caveolin-1 (Cav-1), a major component of caveolae which regulates cell signaling and endocytosis, is a potential target to treat fibrotic diseases, although the mechanisms and responsible cell types are unclear. We show that Cav-1 expression was downregulated both in alveolar epithelial type I cells in bleomycin-injured mouse lungs and in lung sections from IPF patients. Increased expression of IL-1β and caspase-1 has been observed in IPF patients, indicating inflammasome activation associated with IPF. Gene transfer of a plasmid expressing Cav-1 using transthoracic electroporation reduced infiltration of neutrophils and monocytes/macrophages and protected from subsequent bleomycin-induced pulmonary fibrosis. Overexpression of Cav-1 suppressed bleomycin- or silica-induced activation of caspase-1 and maturation of pro-IL-1β to secrete cleaved IL-1β both in mouse lungs and in primary type I cells. These results demonstrate that gene transfer of Cav-1 downregulates inflammasome activity and protects from subsequent bleomycin-mediated pulmonary fibrosis. This indicates a pivotal regulation of Cav-1 in inflammasome activity and suggests a novel therapeutic strategy for patients with IPF.

scholarly journals Pathologic Caveolin-1 Regulation of PTEN in Idiopathic Pulmonary Fibrosis

2010 ◽  
Vol 176 (6) ◽  
pp. 2626-2637 ◽  
Author(s):  
Hong Xia ◽  
Wajahat Khalil ◽  
Judy Kahm ◽  
Jose Jessurun ◽  
Jill Kleidon ◽  
...  
Keyword(s):  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Caveolin 1

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.

Late Breaking Abstract - Caveolin-1 derived peptide LTI-03 promotes epithelial cell survival and attenuates pulmonary fibrosis

2019 ◽  
Author(s):  
BreAnne MacKenzie ◽  
Venkadesa Gopal ◽  
Liang Fan ◽  
Esther Maier ◽  
Yajie Zhang ◽  
...  
Keyword(s):  
Epithelial Cell ◽  
Pulmonary Fibrosis ◽  
Cell Survival ◽  
Caveolin 1

scholarly journals Caveolin-1 Deficiency Protects from Pulmonary Fibrosis by Modulating Epithelial Cell Senescence in Mice

2012 ◽  
Vol 47 (1) ◽  
pp. 28-36 ◽  
Author(s):  
Pooja Shivshankar ◽  
Christopher Brampton ◽  
Shelley Miyasato ◽  
Michael Kasper ◽  
Victor J. Thannickal ◽  
...  
Keyword(s):  
Epithelial Cell ◽  
Pulmonary Fibrosis ◽  
Cell Senescence ◽  
Caveolin 1

Intratracheal gene transfer of tissue factor pathway inhibitor attenuates pulmonary fibrosis

2006 ◽  
Vol 339 (4) ◽  
pp. 1113-1119 ◽  
Author(s):  
Naoki Kijiyama ◽  
Hikaru Ueno ◽  
Isamu Sugimoto ◽  
Yasuyuki Sasaguri ◽  
Kazuhiro Yatera ◽  
...  
Keyword(s):  
Gene Transfer ◽  
Pulmonary Fibrosis ◽  
Tissue Factor ◽  
Tissue Factor Pathway Inhibitor ◽  
Tissue Factor Pathway

scholarly journals COVID-19: Immunohistochemical Analysis of TGF-β Signaling Pathways in Pulmonary Fibrosis

2021 ◽  
Vol 23 (1) ◽  
pp. 168
Author(s):  
Caroline Busatta Vaz de Vaz de Paula ◽  
Seigo Nagashima ◽  
Vanessa Liberalesso ◽  
Mariana Collete ◽  
Felipe Paes Gomes da da Silva ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Signaling Pathways ◽  
Diffuse Alveolar Damage ◽  
Life Quality ◽  
Immunohistochemical Analysis ◽  
Tissue Expression ◽  
Control Group ◽  
Caveolin 1 ◽  
Injury Control ◽  
Tgf Β1

Acute respiratory distress syndrome (ARDS) followed by repair with lung remodeling is observed in COVID-19. These findings can lead to pulmonary terminal fibrosis, a form of irreversible sequelae. There is evidence that TGF-β is intimately involved in the fibrogenic process. When activated, TGF-β promotes the differentiation of fibroblasts into myofibroblasts and regulates the remodeling of the extracellular matrix (ECM). In this sense, the present study evaluated the histopathological features and immunohistochemical biomarkers (ACE-2, AKT-1, Caveolin-1, CD44v6, IL-4, MMP-9, α-SMA, Sphingosine-1, and TGF-β1 tissue expression) involved in the TGF-β1 signaling pathways and pulmonary fibrosis. The study consisted of 24 paraffin lung samples from patients who died of COVID-19 (COVID-19 group), compared to 10 lung samples from patients who died of H1N1pdm09 (H1N1 group) and 11 lung samples from patients who died of different causes, with no lung injury (CONTROL group). In addition to the presence of alveolar septal fibrosis, diffuse alveolar damage (DAD) was found to be significantly increased in the COVID-19 group, associated with a higher density of Collagen I (mature) and III (immature). There was also a significant increase observed in the immunoexpression of tissue biomarkers ACE-2, AKT-1, CD44v6, IL-4, MMP-9, α-SMA, Sphingosine-1, and TGF-β1 in the COVID-19 group. A significantly lower expression of Caveolin-1 was also found in this group. The results suggest the participation of TGF-β pathways in the development process of pulmonary fibrosis. Thus, it would be plausible to consider therapy with TGF-β inhibitors in those patients recovered from COVID-19 to mitigate a possible development of pulmonary fibrosis and its consequences for post-COVID-19 life quality.

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