The Multi-Faceted Extracellular Matrix: Unlocking Its Secrets for Understanding the Perpetuation of Lung Fibrosis

2022 ◽  
Author(s):  
Mehmet Nizamoglu ◽  
Janette K. Burgess
Keyword(s):  
Extracellular Matrix ◽  
Lung Fibrosis

Three-dimensional investigation and scoring of extracellular matrix remodeling during lung fibrosis using multiphoton microscopy

2007 ◽  
Vol 70 (2) ◽  
pp. 162-170 ◽  
Author(s):  
Ana-Maria Pena ◽  
Aurélie Fabre ◽  
Delphine Débarre ◽  
Joëlle Marchal-Somme ◽  
Bruno Crestani ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Lung Fibrosis ◽  
Multiphoton Microscopy ◽  
Three Dimensional ◽  
Extracellular Matrix Remodeling ◽  
Matrix Remodeling

Glutathione peroxidase 3 localizes to the epithelial lining fluid and the extracellular matrix in lung fibrosis

2016 ◽  
Author(s):  
Andrea Schamberger ◽  
Herbert Schiller ◽  
Isis Fernandez ◽  
Martina Sterclova ◽  
Katharina Heinzelmann ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Glutathione Peroxidase ◽  
Lung Fibrosis ◽  
Epithelial Lining ◽  
Epithelial Lining Fluid ◽  
Glutathione Peroxidase 3

Connective-Tissue Growth Factor (CTGF/CCN2) Contributes to TGF-β1-Induced Lung Fibrosis

2020 ◽  
Author(s):  
Toyoshi Yanagihara ◽  
Sy Giin Chong ◽  
Mahsa Gholiof ◽  
Kenneth E. Lipson ◽  
Quan Zhou ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Growth Factor ◽  
Connective Tissue ◽  
Pulmonary Fibrosis ◽  
Connective Tissue Growth Factor ◽  
Lung Fibrosis ◽  
Adenovirus Vector ◽  
Tissue Growth ◽  
Inhibitory Antibody ◽  
Tgf Β1

AbstractIdiopathic pulmonary fibrosis (IPF) is a fatal lung disease characterized by progressive and excessive accumulation of myofibroblasts and extracellular matrix in the lung. Connective-tissue growth factor (CTGF) is known to exacerbate pulmonary fibrosis in radiation-induced lung fibrosis, and in this study, we show the upregulation of CTGF from a rat lung fibrosis model induced by adenovirus vector encoding active TGF-β1 (AdTGF-β1), and also in patients with IPF. The expression of CTGF was upregulated in vascular smooth muscle cells cultured from fibrotic lungs on days 7 or 14 as well as endothelial cells sorted from fibrotic lungs on day 14 or 28 respectively. These findings suggest the role of different cells in maintaining the fibrotic phenotype during fibrogenesis. Treatment of fibroblasts with recombinant CTGF along with TGF-β increases pro-fibrotic markers in fibroblasts, confirming the synergistic effect of recombinant CTGF with TGF-β in inducing pulmonary fibrosis. Also, fibrotic extracellular matrix upregulated the expression of CTGF, as compared to normal extracellular matrix, suggesting that not only profibrotic mediators but also a profibrotic environment contributes to fibrogenesis. We also showed that pamrevlumab, a CTGF inhibitory antibody, partially attenuates fibrosis in the model. These results suggest that pamrevlumab could be an option for the treatment of pulmonary fibrosis.

scholarly journals NADPH oxidase DUOX1 sustains TGF-β1 signalling and promotes lung fibrosis

2020 ◽  
pp. 1901949
Author(s):  
Ruy Andrade Louzada ◽  
Raphaël Corre ◽  
Rabii Ameziane El Hassani ◽  
Lydia Meziani ◽  
Madeleine Jaillet ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Pulmonary Fibrosis ◽  
Nadph Oxidase ◽  
Lung Fibrosis ◽  
Transforming Growth Factor ◽  
Lung Fibroblasts ◽  
Mouse Lung ◽  
Epithelial Surface ◽  
Tgf Β1

Interstitial lung fibroblast activation coupled with extracellular matrix production is a pathological signature of pulmonary fibrosis, and is governed by transforming growth factor (TGF-β1)/Smad signalling. TGF-β1 and oxidative stress cooperate to drive fibrosis. Cells can produce reactive oxygen species (ROS) through activation and/or induction of NADPH oxidases, such as dual oxidase (DUOX1/2). Since DUOX enzymes, as extracellular H2O2-generating systems, are involved in extracellular matrix formation and in wound healing in different experimental models, we hypothesised that DUOX-based NADPH oxidase plays a role in the pathophysiology of pulmonary fibrosis.Our in vivo data (IPF patients and mouse models of lung fibrosis) showed that the NADPH oxidase DUOX1 is induced in response to lung injury. DUOX1-deficient mice (DUOX1+/- and DUOX1-/-) had an attenuated fibrotic phenotype. In addition to being highly expressed at the epithelial surface of airways, DUOX1 appears to be also well expressed in the fibroblastic foci of remodelled lungs. By using primary human and mouse lung fibroblasts, we showed that TGF-β1 upregulates DUOX1 and its maturation factor DUOXA1 and that DUOX1-derived H2O2 promoted the duration of TGF-β1-activated Smad3 phosphorylation by preventing phospho-Smad3 degradation. Analysis of the mechanism revealed that DUOX1 inhibited the interaction between phospho-Smad3 and the ubiquitin ligase NEDD4L, preventing NEDD4L-mediated ubiquitination of phospho-Smad3 and its targeting for degradation.These findings highlight a role for DUOX1-derived H2O2 in a positive feedback that amplifies the signalling output of the TGF-β1 pathway and identify DUOX1 as a new therapeutic target in pulmonary fibrosis.

scholarly journals TRPV4 Mechanotransduction in Fibrosis

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 3053
Author(s):  
Ravi K. Adapala ◽  
Venkatesh Katari ◽  
Lakshminarayan Reddy Teegala ◽  
Sathwika Thodeti ◽  
Sailaja Paruchuri ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Organ Failure ◽  
Therapeutic Target ◽  
Lung Fibrosis ◽  
Mechanical Factors

Fibrosis is an irreversible, debilitating condition marked by the excessive production of extracellular matrix and tissue scarring that eventually results in organ failure and disease. Differentiation of fibroblasts to hypersecretory myofibroblasts is the key event in fibrosis. Although both soluble and mechanical factors are implicated in fibroblast differentiation, much of the focus is on TGF-β signaling, but to date, there are no specific drugs available for the treatment of fibrosis. In this review, we describe the role for TRPV4 mechanotransduction in cardiac and lung fibrosis, and we propose TRPV4 as an alternative therapeutic target for fibrosis.

scholarly journals Relaxin induces an extracellular matrix-degrading phenotype in human lung fibroblasts in vitro and inhibits lung fibrosis in a murine model in vivo.

1996 ◽  
Vol 98 (12) ◽  
pp. 2739-2745 ◽  
Author(s):  
E N Unemori ◽  
L B Pickford ◽  
A L Salles ◽  
C E Piercy ◽  
B H Grove ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Murine Model ◽  
Lung Fibrosis ◽  
Human Lung ◽  
Lung Fibroblasts ◽  
Human Lung Fibroblasts

Changes in Extracellular Matrix and Tissue Viscoelasticity in Bleomycin–induced Lung Fibrosis

2000 ◽  
Vol 162 (4) ◽  
pp. 1569-1576 ◽  
Author(s):  
TAKAE EBIHARA ◽  
NARAYANAN VENKATESAN ◽  
RYOICHI TANAKA ◽  
MARA S. LUDWIG
Keyword(s):  
Extracellular Matrix ◽  
Lung Fibrosis
Sign in / Sign up

Export Citation Format

Share Document