β-Catenin Signaling in Fibroproliferative Disease

Bowley, Erin; O’Gorman, David B.; Gan, Bing Siang

doi:10.1016/j.jss.2006.07.026

Cited by 101 publications

(87 citation statements)

References 112 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…While β-catenin is best recognised as a component of the Wnt/frizzled signalling pathway, [15,21], additional roles for β-catenin in the transforming growth factor (TGF)-β1 [22][23][24] and oxidative stress-activated [21] pathways have been described. β-catenin is also an integral component of adherens junctions [15,25]; cell-membrane-associated structures that myo broblasts use during cell to cell interactions to promote extra-cellular matrix contraction and remodelling during brosis development [26].…”

Section: Discussionmentioning

confidence: 99%

“…As FSS and DD are clinically associated [3,20], we were interested to see if these characteristics were common to both connective tissue broses. Our ndings indicate that increased IGF2 expression and β-catenin accumulation are also evident in FSS, supporting the hypothesis that these connective tissue broses share a common pathophysiology.While β-catenin is best recognised as a component of the Wnt/frizzled signalling pathway, [15,21], additional roles for β-catenin in the transforming growth factor (TGF)-β1 [22][23][24] and oxidative stress-activated [21] pathways have been described. β-catenin is also an integral component of adherens junctions [15,25]; cell-membrane-associated structures that myo broblasts use during cell to cell interactions to promote extra-cellular matrix contraction and remodelling during brosis development [26].…”

mentioning

confidence: 99%

See 1 more Smart Citation

IGF2 expression and β-catenin levels are increased in Frozen Shoulder Syndrome

Raykha¹,

Crawford²,

Burry³

et al. 2014

CIM

Self Cite

View full text Add to dashboard Cite

IGF2 expression and β-catenin levels are increased in Frozen Shoulder Syndrome Abstract Purpose: Frozen Shoulder Syndrome is a brosis of the shoulder joint capsule that is clinically associated with Dupuytren's disease, a brosis of the palmar fascia. Little is known about any commonalities in the pathophysiology of these connective tissue broses. β-catenin, a protein that transactivates gene expression, and levels of IGF2 mRNA, encoding insulin-like growth factor-II, are elevated in Dupuytren's disease. e aim of this study was to determine if correlating changes in β-catenin levels and IGF2 expression are evident in Frozen Shoulder Syndrome.Methods: Tissue from patients with Frozen Shoulder Syndrome and rotator cu tear were obtained during shoulder arthroscopies. Total protein extracts were prepared from tissue aliquots and β-catenin immunoreactivity was assessed by Western immunoblotting. In parallel, primary broblasts were derived from these tissues and assessed for IGF2 expression by quantitative PCR.Results: β-catenin levels were signi cantly increased in Frozen Shoulder Syndrome relative to rotator cu tear when assessed by Western immunoblotting analyses. IGF2 mRNA levels were signi cantly increased in primary broblasts derived from frozen shoulder syndrome tissues relative to broblasts derived from rotator cu tissues. Conclusions:As in Dupuytren's disease, β-catenin levels and IGF2 expression are elevated in Frozen Shoulder Syndrome. ese ndings support the hypothesis that these connective tissue broses share a common pathophysiology. Materials and Methods Tissue collectionTissue sections were collected with approval of the Human Subjects Research Ethics Board (HSREB) at Western University from surgical specimens of patients undergoing shoulder arthroscopy for the treatment of either FSS or subacromial decompression for RCT. An arthroscopic punch was used to obtain tissue specimens from the rotator cu interval immediately adjacent to the antero-superior arthroscopic portal from patients with FSS and RCT. Representative samples of these tissues were removed at the time of surgery and immediately transported to the laboratory. e tissues were either snap frozen in liquid nitrogen for total protein extraction or processed for primary broblast derivation. Western immunoblottingTotal protein extracts were prepared from snap frozen tissue using modi ed RIPA bu er. Tissue lysate (25 μg) was subjected to Western blot analysis and β-catenin levels were assessed using an anti-β-catenin monoclonal antibody (clone 14, Transduction Laboratories, Lexington, KY). β-actin levels were assessed in parallel using an anti-β-actin antibody (Sigma, St Louis, MO) to normalize for variability in total protein loading. Antibody speci c bands were visualized using enhanced chemiluminescence (ECL) and Kodak XLS lm. Densitometry analysis was carried out using Scion Image so ware (Scion Corporation, Beta 4.0.2, Frederick, MD). Normalized measurements of β-catenin were plotted as the sample mean (β-catenin /actin) ratio ± standard error...

show abstract

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

IGF2 expression and β-catenin levels are increased in Frozen Shoulder Syndrome

Raykha¹,

Crawford²,

Burry³

et al. 2014

CIM

Self Cite

View full text Add to dashboard Cite

show abstract

“…26 Elevated levels of b-catenin have been reported in Dupuytren's contracture without involvement of b-catenin mutations. 27 Possible mechanisms explaining b-catenin accumulation include alterations in the Wnt/b-catenin signaling pathway, which makes it potentially the most important pathway involved in Dupuytren's contracture pathogenesis.…”

mentioning

confidence: 99%

Unique microRNA profile in Dupuytren's contracture supports deregulation of β-catenin pathway

et al. 2010

View full text Add to dashboard Cite

“…It is well known that this pathway is abnormally activated in several human cancers, including lung cancer, mesothelioma and desmoid tumours [51]. More recently, an activation of the Wnt/b-catenin pathway has been also described in different fibroproliferative disorders of the liver and kidney [52]. In regard to this, CHILOSI et al [53] have shown that the Wnt/b-catenin pathway is strongly activated in IPF lung tissues as demonstrated by the presence of an intense immunoreactivity for b-catenin and a contemporary expression of high levels of two downstream genes of the Wnt/b-catenin pathway, cyclin-D1 and matrilysin.…”

Section: Abnormal Activation Of Specific Signalling Pathwaysmentioning

confidence: 99%

A progression-free end-point for idiopathic pulmonary fibrosis trials: lessons from cancer

Vancheri

Bois

2012

Eur Respir J

View full text Add to dashboard Cite

Idiopathic pulmonary fibrosis (IPF) is a progressive fibroproliferative disease that results in increasing morbidity. To date there is only one licensed therapy for this condition and other agents are needed for this attritional disease. Efforts to study other agents have been obstructed by an increasing division of opinion about the most clinically meaningful end-point of phase III clinical trials to demonstrate efficacy. Many clinicians believe that an agent that impedes progression of the disease is more than acceptable and will encourage the pharmaceutical industry to further develop their IPF programmes. We have been impressed by the behavioural and biological similarities of cancer and IPF, and wondered if lessons could be learned about clinical trial design from lung cancer studies. Here, we set out our arguments that the similarities with cancer justify comparing the magnitude of therapeutic effects in clinical trials in nonsmall cell lung cancer with those in successful trials in IPF. We demonstrate that efficacy is of a similar magnitude in the two chronic lung diseases. We recommend that the demonstration of similar magnitudes of progression-free disease effect in IPF, using appropriate indices, should be considered as clinically meaningful benefit in future phase III clinical trials of novel therapies.KEYWORDS: Clinical trials, fibroblast/myofibroblast, forced vital capacity, lung cancer, pulmonary fibrosis, pulmonary function tests I diopathic pulmonary fibrosis (IPF) is a progressive fibroproliferative disease characterised by an accumulation of myofibroblasts in the alveolar wall, aberrant matrix deposition and subsequent distortion of the normal lung architecture. The disease results in progressive morbidity, worsening quality of life and an increasing dependence on others for the most basic of functional needs. The current paradigm of the pathogenetic process that results in IPF is that the disease is initiated by recurrent injury to the alveolar epithelium and evolves into an aberrant fibroproliferative response which progresses [1]. The cause(s) of the repeated injury is unknown but is thought to be the product of one or more environmental triggers operating within an individual whose genotype makes them susceptible to the disease [2]. More recently, IPF has been assimilated to a neoproliferative disorder based on the evidence that a number of pathogenic features of IPF are shared with cancer biology [3]. Genetic and epigenetic changes, delayed apoptosis and altered response to regulatory signals by myofibroblasts, reduced cellular communications and abnormal activation of specific signalling pathways have been shown to be hallmarks common to IPF and cancer. Consistent with this, COOL et al. [4] reported that ''fibroblast foci'', the characteristic defining lesions in IPF, are interconnected, forming a three-dimensional reticulum that resembles the tissue infiltration typical of cancer. The absence of monoclonality noted within the fibroblast foci and their incapacity to metastasise ...

show abstract

β-Catenin Signaling in Fibroproliferative Disease

Cited by 101 publications

References 112 publications

IGF2 expression and β-catenin levels are increased in Frozen Shoulder Syndrome

IGF2 expression and β-catenin levels are increased in Frozen Shoulder Syndrome

Unique microRNA profile in Dupuytren's contracture supports deregulation of β-catenin pathway

A progression-free end-point for idiopathic pulmonary fibrosis trials: lessons from cancer

Contact Info

Product

Resources

About