Aberrant Wnt/β-Catenin Pathway Activation in Idiopathic Pulmonary Fibrosis
To investigate the molecular events that may underpin dysfunctional repair processes that characterize idiopathic pulmonary fibrosis/usual interstitial pneumonia (IPF/UIP), we analyzed the expression patterns of β-catenin on 20 IPF/UIP lung samples, together with two downstream target genes of Wnt s...
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creator | Chilosi, Marco Poletti, Venerino Zamò, Alberto Lestani, Maurizio Montagna, Licia Piccoli, Paola Pedron, Serena Bertaso, Manuela Scarpa, Aldo Murer, Bruno Cancellieri, Alessandra Maestro, Roberta Semenzato, Gianpietro Doglioni, Claudio |
description | To investigate the molecular events that may underpin dysfunctional repair processes that characterize idiopathic pulmonary fibrosis/usual interstitial pneumonia (IPF/UIP), we analyzed the expression patterns of β-catenin on 20 IPF/UIP lung samples, together with two downstream target genes of Wnt signaling, cyclin-D1, and matrilysin. In 18 of 20 cases of IPF/UIP investigated on serial sections, nuclear β-catenin immunoreactivity and abnormal levels of cyclin-D1 and matrilysin were demonstrated in proliferative bronchiolar lesions (basal-cell hyperplasia, squamous metaplasia, bronchiolization, honeycombing). The nature of these lesions was precisely defined using specific markers (ΔN-p63, surfactant-protein-A, cytokeratin-5). Interestingly, nuclear β-catenin accumulation was also demonstrated in fibroblast foci in most (16 of 20) IPF/UIP samples, often associated with bronchiolar lesions. Similar features were not observed in normal lung and other fibrosing pulmonary diseases (diffuse alveolar damage, organizing pneumonia, nonspecific interstitial pneumonia, desquamative interstitial pneumonia). Sequence analysis performed on DNA extracted from three samples of IPF/UIP did not reveal abnormalities affecting the β-catenin gene. On the basis of these findings new models for IPF/UIP pathogenesis can be hypothesized, centered on the aberrant activation of Wnt/β-catenin signaling, with eventual triggering of divergent epithelial regeneration at bronchiolo-alveolar junctions and epithelial-mesenchymal-transitions, leading to severe and irreversible remodeling of the pulmonary tissue. |
doi_str_mv | 10.1016/S0002-9440(10)64282-4 |
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In 18 of 20 cases of IPF/UIP investigated on serial sections, nuclear β-catenin immunoreactivity and abnormal levels of cyclin-D1 and matrilysin were demonstrated in proliferative bronchiolar lesions (basal-cell hyperplasia, squamous metaplasia, bronchiolization, honeycombing). The nature of these lesions was precisely defined using specific markers (ΔN-p63, surfactant-protein-A, cytokeratin-5). Interestingly, nuclear β-catenin accumulation was also demonstrated in fibroblast foci in most (16 of 20) IPF/UIP samples, often associated with bronchiolar lesions. Similar features were not observed in normal lung and other fibrosing pulmonary diseases (diffuse alveolar damage, organizing pneumonia, nonspecific interstitial pneumonia, desquamative interstitial pneumonia). Sequence analysis performed on DNA extracted from three samples of IPF/UIP did not reveal abnormalities affecting the β-catenin gene. On the basis of these findings new models for IPF/UIP pathogenesis can be hypothesized, centered on the aberrant activation of Wnt/β-catenin signaling, with eventual triggering of divergent epithelial regeneration at bronchiolo-alveolar junctions and epithelial-mesenchymal-transitions, leading to severe and irreversible remodeling of the pulmonary tissue.</description><identifier>ISSN: 0002-9440</identifier><identifier>EISSN: 1525-2191</identifier><identifier>DOI: 10.1016/S0002-9440(10)64282-4</identifier><identifier>PMID: 12707032</identifier><identifier>CODEN: AJPAA4</identifier><language>eng</language><publisher>Bethesda, MD: Elsevier Inc</publisher><subject>Adult ; beta Catenin ; Biological and medical sciences ; Cytoskeletal Proteins - genetics ; Fetus ; Gene Expression Regulation ; Humans ; Lung - embryology ; Medical sciences ; Pneumology ; Proto-Oncogene Proteins - genetics ; Pulmonary Fibrosis - genetics ; Pulmonary Fibrosis - pathology ; Regular ; Respiratory system : syndromes and miscellaneous diseases ; Trans-Activators - genetics ; Wnt Proteins ; Zebrafish Proteins</subject><ispartof>The American journal of pathology, 2003-05, Vol.162 (5), p.1495-1502</ispartof><rights>2003 American Society for Investigative Pathology</rights><rights>2003 INIST-CNRS</rights><rights>Copyright © 2003, American Society for Investigative Pathology</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c545t-9425c5a714a3582b841a193f68722928fb83e0ac00eb6993c1a44889d0c4f1453</citedby><cites>FETCH-LOGICAL-c545t-9425c5a714a3582b841a193f68722928fb83e0ac00eb6993c1a44889d0c4f1453</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1851206/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://dx.doi.org/10.1016/S0002-9440(10)64282-4$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,315,729,782,786,887,3552,27931,27932,46002,53798,53800</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=14737096$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12707032$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chilosi, Marco</creatorcontrib><creatorcontrib>Poletti, Venerino</creatorcontrib><creatorcontrib>Zamò, Alberto</creatorcontrib><creatorcontrib>Lestani, Maurizio</creatorcontrib><creatorcontrib>Montagna, Licia</creatorcontrib><creatorcontrib>Piccoli, Paola</creatorcontrib><creatorcontrib>Pedron, Serena</creatorcontrib><creatorcontrib>Bertaso, Manuela</creatorcontrib><creatorcontrib>Scarpa, Aldo</creatorcontrib><creatorcontrib>Murer, Bruno</creatorcontrib><creatorcontrib>Cancellieri, Alessandra</creatorcontrib><creatorcontrib>Maestro, Roberta</creatorcontrib><creatorcontrib>Semenzato, Gianpietro</creatorcontrib><creatorcontrib>Doglioni, Claudio</creatorcontrib><title>Aberrant Wnt/β-Catenin Pathway Activation in Idiopathic Pulmonary Fibrosis</title><title>The American journal of pathology</title><addtitle>Am J Pathol</addtitle><description>To investigate the molecular events that may underpin dysfunctional repair processes that characterize idiopathic pulmonary fibrosis/usual interstitial pneumonia (IPF/UIP), we analyzed the expression patterns of β-catenin on 20 IPF/UIP lung samples, together with two downstream target genes of Wnt signaling, cyclin-D1, and matrilysin. In 18 of 20 cases of IPF/UIP investigated on serial sections, nuclear β-catenin immunoreactivity and abnormal levels of cyclin-D1 and matrilysin were demonstrated in proliferative bronchiolar lesions (basal-cell hyperplasia, squamous metaplasia, bronchiolization, honeycombing). The nature of these lesions was precisely defined using specific markers (ΔN-p63, surfactant-protein-A, cytokeratin-5). Interestingly, nuclear β-catenin accumulation was also demonstrated in fibroblast foci in most (16 of 20) IPF/UIP samples, often associated with bronchiolar lesions. Similar features were not observed in normal lung and other fibrosing pulmonary diseases (diffuse alveolar damage, organizing pneumonia, nonspecific interstitial pneumonia, desquamative interstitial pneumonia). Sequence analysis performed on DNA extracted from three samples of IPF/UIP did not reveal abnormalities affecting the β-catenin gene. On the basis of these findings new models for IPF/UIP pathogenesis can be hypothesized, centered on the aberrant activation of Wnt/β-catenin signaling, with eventual triggering of divergent epithelial regeneration at bronchiolo-alveolar junctions and epithelial-mesenchymal-transitions, leading to severe and irreversible remodeling of the pulmonary tissue.</description><subject>Adult</subject><subject>beta Catenin</subject><subject>Biological and medical sciences</subject><subject>Cytoskeletal Proteins - genetics</subject><subject>Fetus</subject><subject>Gene Expression Regulation</subject><subject>Humans</subject><subject>Lung - embryology</subject><subject>Medical sciences</subject><subject>Pneumology</subject><subject>Proto-Oncogene Proteins - genetics</subject><subject>Pulmonary Fibrosis - genetics</subject><subject>Pulmonary Fibrosis - pathology</subject><subject>Regular</subject><subject>Respiratory system : syndromes and miscellaneous diseases</subject><subject>Trans-Activators - genetics</subject><subject>Wnt Proteins</subject><subject>Zebrafish Proteins</subject><issn>0002-9440</issn><issn>1525-2191</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc1O3DAUha2qCIYpj9Aqm1awSPFv4mxAoxF_KlKR2qpL68ZxiquMPdieqXgtHoRnwmFG0K66snzvd6-Pz0HoPcGfCSbV8TeMMS0bzvEhwUcVp5KW_A2aEEFFSUlD3qLJC7KH9mP8na8Vk3gX7RFa4xozOkFfZq0JAVwqfrp0_PhQziEZZ11xA-n2D9wXM53sGpL1rsjVq876Ze5YXdyshoV3EO6Lc9sGH218h3Z6GKI52J5T9OP87Pv8srz-enE1n12XWnCRsiAqtICacGBC0lZyAqRhfSVrShsq-1Yyg0FjbNqqaZgmwLmUTYc17wkXbIpONnuXq3ZhOm1cCjCoZbCLLEd5sOrfjrO36pdfKyIFodmDKfq0XRD83crEpBY2ajMM4IxfRVWzLESwERQbUOcPxmD6l0cIVmMM6jkGNXo8lp5jUDzPffhb4evU1vcMfNwCEDUMfU5A2_jK8ZrVuBkFnG44k_1cWxNU1NY4bTobjE6q8_Y_Up4AU-2ksQ</recordid><startdate>20030501</startdate><enddate>20030501</enddate><creator>Chilosi, Marco</creator><creator>Poletti, Venerino</creator><creator>Zamò, Alberto</creator><creator>Lestani, Maurizio</creator><creator>Montagna, Licia</creator><creator>Piccoli, Paola</creator><creator>Pedron, Serena</creator><creator>Bertaso, Manuela</creator><creator>Scarpa, Aldo</creator><creator>Murer, Bruno</creator><creator>Cancellieri, Alessandra</creator><creator>Maestro, Roberta</creator><creator>Semenzato, Gianpietro</creator><creator>Doglioni, Claudio</creator><general>Elsevier Inc</general><general>American Society for Investigative Pathology</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20030501</creationdate><title>Aberrant Wnt/β-Catenin Pathway Activation in Idiopathic Pulmonary Fibrosis</title><author>Chilosi, Marco ; Poletti, Venerino ; Zamò, Alberto ; Lestani, Maurizio ; Montagna, Licia ; Piccoli, Paola ; Pedron, Serena ; Bertaso, Manuela ; Scarpa, Aldo ; Murer, Bruno ; Cancellieri, Alessandra ; Maestro, Roberta ; Semenzato, Gianpietro ; Doglioni, Claudio</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c545t-9425c5a714a3582b841a193f68722928fb83e0ac00eb6993c1a44889d0c4f1453</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Adult</topic><topic>beta Catenin</topic><topic>Biological and medical sciences</topic><topic>Cytoskeletal Proteins - genetics</topic><topic>Fetus</topic><topic>Gene Expression Regulation</topic><topic>Humans</topic><topic>Lung - embryology</topic><topic>Medical sciences</topic><topic>Pneumology</topic><topic>Proto-Oncogene Proteins - genetics</topic><topic>Pulmonary Fibrosis - genetics</topic><topic>Pulmonary Fibrosis - pathology</topic><topic>Regular</topic><topic>Respiratory system : syndromes and miscellaneous diseases</topic><topic>Trans-Activators - genetics</topic><topic>Wnt Proteins</topic><topic>Zebrafish Proteins</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chilosi, Marco</creatorcontrib><creatorcontrib>Poletti, Venerino</creatorcontrib><creatorcontrib>Zamò, Alberto</creatorcontrib><creatorcontrib>Lestani, Maurizio</creatorcontrib><creatorcontrib>Montagna, Licia</creatorcontrib><creatorcontrib>Piccoli, Paola</creatorcontrib><creatorcontrib>Pedron, Serena</creatorcontrib><creatorcontrib>Bertaso, Manuela</creatorcontrib><creatorcontrib>Scarpa, Aldo</creatorcontrib><creatorcontrib>Murer, Bruno</creatorcontrib><creatorcontrib>Cancellieri, Alessandra</creatorcontrib><creatorcontrib>Maestro, Roberta</creatorcontrib><creatorcontrib>Semenzato, Gianpietro</creatorcontrib><creatorcontrib>Doglioni, Claudio</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The American journal of pathology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chilosi, Marco</au><au>Poletti, Venerino</au><au>Zamò, Alberto</au><au>Lestani, Maurizio</au><au>Montagna, Licia</au><au>Piccoli, Paola</au><au>Pedron, Serena</au><au>Bertaso, Manuela</au><au>Scarpa, Aldo</au><au>Murer, Bruno</au><au>Cancellieri, Alessandra</au><au>Maestro, Roberta</au><au>Semenzato, Gianpietro</au><au>Doglioni, Claudio</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Aberrant Wnt/β-Catenin Pathway Activation in Idiopathic Pulmonary Fibrosis</atitle><jtitle>The American journal of pathology</jtitle><addtitle>Am J Pathol</addtitle><date>2003-05-01</date><risdate>2003</risdate><volume>162</volume><issue>5</issue><spage>1495</spage><epage>1502</epage><pages>1495-1502</pages><issn>0002-9440</issn><eissn>1525-2191</eissn><coden>AJPAA4</coden><abstract>To investigate the molecular events that may underpin dysfunctional repair processes that characterize idiopathic pulmonary fibrosis/usual interstitial pneumonia (IPF/UIP), we analyzed the expression patterns of β-catenin on 20 IPF/UIP lung samples, together with two downstream target genes of Wnt signaling, cyclin-D1, and matrilysin. In 18 of 20 cases of IPF/UIP investigated on serial sections, nuclear β-catenin immunoreactivity and abnormal levels of cyclin-D1 and matrilysin were demonstrated in proliferative bronchiolar lesions (basal-cell hyperplasia, squamous metaplasia, bronchiolization, honeycombing). The nature of these lesions was precisely defined using specific markers (ΔN-p63, surfactant-protein-A, cytokeratin-5). Interestingly, nuclear β-catenin accumulation was also demonstrated in fibroblast foci in most (16 of 20) IPF/UIP samples, often associated with bronchiolar lesions. Similar features were not observed in normal lung and other fibrosing pulmonary diseases (diffuse alveolar damage, organizing pneumonia, nonspecific interstitial pneumonia, desquamative interstitial pneumonia). Sequence analysis performed on DNA extracted from three samples of IPF/UIP did not reveal abnormalities affecting the β-catenin gene. On the basis of these findings new models for IPF/UIP pathogenesis can be hypothesized, centered on the aberrant activation of Wnt/β-catenin signaling, with eventual triggering of divergent epithelial regeneration at bronchiolo-alveolar junctions and epithelial-mesenchymal-transitions, leading to severe and irreversible remodeling of the pulmonary tissue.</abstract><cop>Bethesda, MD</cop><pub>Elsevier Inc</pub><pmid>12707032</pmid><doi>10.1016/S0002-9440(10)64282-4</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Adult beta Catenin Biological and medical sciences Cytoskeletal Proteins - genetics Fetus Gene Expression Regulation Humans Lung - embryology Medical sciences Pneumology Proto-Oncogene Proteins - genetics Pulmonary Fibrosis - genetics Pulmonary Fibrosis - pathology Regular Respiratory system : syndromes and miscellaneous diseases Trans-Activators - genetics Wnt Proteins Zebrafish Proteins |
title | Aberrant Wnt/β-Catenin Pathway Activation in Idiopathic Pulmonary Fibrosis |
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