Epithelial–mesenchymal transition in human lungs with usual interstitial pneumonia: Quantitative immunohistochemistry

Harada, Taishi; Nabeshima, Kazuki; Hamasaki, Makoto; Uesugi, Noriko; Watanabe, Kentaro; Iwasaki, Hiroshi

doi:10.1111/j.1440-1827.2009.02469.x

Cited by 38 publications

(36 citation statements)

References 34 publications

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“…In this and other studies, immunohistochemical analysis of a limited number of IPF lung tissue samples has provided indirect evidence for the occurrence of EMT as shown by the co-expression of mesenchymal and epithelial markers in epithelial cells, which was not observed in control lungs [72][73][74]. Unfortunately, the only study that included patients with UIP or NSIP is also the only investigation not to find any evidence of EMT in either of the patient groups or in controls [75].…”

Section: Epithelial-mesenchymal Transitionmentioning

confidence: 73%

Idiopathic Pulmonary Fibrosis—an Epidemiological and Pathological Review

Borchers

Chang²,

Keen

et al. 2010

Clinic Rev Allerg Immunol

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Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease (ILD) affecting the pulmonary interstitium. Other forms of interstitial lung disease exist, and in some cases, an environmental etiology can be delineated. The diagnosis of IPF is typically established by high-resolution CT scan. IPF tends to have a worse prognosis than other forms of ILD. Familial cases of IPF also exist, suggesting a genetic predisposition; telomerase mutations have been observed to occur in familial IPF, which may also explain the increase in IPF with advancing age. Alveolar epithelial cells are believed to be the primary target of environmental agents that have been putatively associated with IPF. These agents may include toxins, viruses, or the autoantibodies found in collagen vascular diseases. The mechanism of disease is still unclear in IPF, but aberrations in fibroblast differentiation, activation, and proliferation may play a role. Epithelial-mesenchymal transition may also be an important factor in the pathogenesis, as it may lead to accumulation of fibroblasts in the lung and a disruption of normal tissue structure. Abnormalities in other components of the immune system, including T cells, B cells, and dendritic cells, as well as the development of ectopic lymphoid tissue, have also been observed to occur in IPF and may play a role in the stimulation of fibrosis that is a hallmark of the disease. It is becoming increasingly clear that the pathogenesis of IPF is indeed a complex and convoluted process that involves numerous cell types and humoral factors.

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Section: Epithelial-mesenchymal Transitionmentioning

confidence: 73%

Idiopathic Pulmonary Fibrosis—an Epidemiological and Pathological Review

Borchers

Chang²,

Keen

et al. 2010

Clinic Rev Allerg Immunol

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“…There have been a number of studies that have tried to characterise molecular endotypes in ILD [7,[30][31][32]. The phenotype, which has been consistently shown to associate with poor survival on lung biopsy, is the presence of high levels of fibroblastic foci [7,9,32].…”

Section: Discussionmentioning

confidence: 99%

αvβ6 integrin may be a potential prognostic biomarker in interstitial lung disease

et al. 2015

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Idiopathic pulmonary fibrosis (IPF) and fibrotic nonspecific interstitial pneumonitis are progressive interstitial lung diseases (ILDs) with limited treatment options and poor survival. However, the rate of disease progression is variable, implying there may be different endotypes of disease. We hypothesised that immunophenotyping biopsies from ILD patients might reveal distinct endotypes of progressive fibrotic disease, which may facilitate stratification when undertaking clinical trials of novel therapies for IPF.43 paraffin-embedded, formalin-fixed lung tissue sections were immunostained for five molecules implicated in the pathogenesis of the fibrosis: α-smooth muscle actin (αSMA), αvβ6 integrin, pro-surfactant protein C (SP-C), hepatocyte growth factor (HGF) and tenascin-C (TenC). Levels of immunostaining and numbers of fibroblastic foci were quantified using operator-dependent and -independent methods. The relationship of all these markers to overall survival was analysed.Staining revealed high levels of αSMA, αvβ6 integrin, pro-SP-C, HGF and TenC, and fibroblastic foci. Immunostaining varied across samples for all molecules but only the extent of αvβ6 integrin immunostaining was associated with increased mortality. There was no association with the other markers measured.Our data suggest high levels of αvβ6 integrin may identify a specific endotype of progressive fibrotic lung disease. @ERSpublications High levels of αvβ6 integrin immunostaining on VATS biopsy predict worse survival than low levels of immunostaining http://ow.ly/IyCfH

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“…According to numerous observations from in vitro studies and some indirect evidence from animal models and human biopsy samples, EMT is widely regarded as contributor to organ fibrosis, e.g., in the liver [10], peritoneal cavity [11], lung [12] and kidney [1][2][3][4]. However, pathologists ''rarely'' identify transition of epithelial cells, meaning catch the moment they pass through the basement membrane in the development of organ fibrosis.…”

Section: Discussionmentioning

confidence: 98%

“…How to reconcile the controversial opinions? Studies have been set up with focus on different organs and epithelial cells from different sources, e.g., hepatocytes from the liver [10], mesothelial cells from peritoneal cavity [11] and alveolar epithelial cells from the lung [12].…”

Section: Review Of the Fieldmentioning

confidence: 99%