Activated Wnt signaling induces myofibroblast differentiation of mesenchymal stem cells, contributing to pulmonary fibrosis
Acute lung injury may lead to fibrogenesis. However, no treatment is currently available. This study was conducted to determine the effects of bone marrow-derived mesenchymal stem cells (MSCs) in a model of HCl-induced acute lung injury in Sprague-Dawley (SD) rats. Stromal cell-derived factor (SDF)-...
Gespeichert in:
| Veröffentlicht in: | International journal of molecular medicine 2014-05, Vol.33 (5), p.1097-1109 |
|---|---|
| Hauptverfasser: | , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 1109 |
|---|---|
| container_issue | 5 |
| container_start_page | 1097 |
| container_title | International journal of molecular medicine |
| container_volume | 33 |
| creator | SUN, ZHAORUI WANG, CONG SHI, CHAOWEN SUN, FANGFANG XU, XIAOMENG QIAN, WEIPING NIE, SHINAN HAN, XIAODONG |
| description | Acute lung injury may lead to fibrogenesis. However, no treatment is currently available. This study was conducted to determine the effects of bone marrow-derived mesenchymal stem cells (MSCs) in a model of HCl-induced acute lung injury in Sprague-Dawley (SD) rats. Stromal cell-derived factor (SDF)-1 and its receptor CXC chemokine receptor (CXCR)4 have been shown to participate in mobilizing MSCs. Adenovirus carrying the CXCR4 gene was used to transfect MSCs in order to increase the engraftment numbers of MSCs at injured sites. Histological examination data demonstrated that the engraftment of MSCs did not attenuate lung injury and pulmonary fibrosis. The results showed that engraftment of MSCs almost differentiated into myofibroblasts, but rarely differentiated into lung epithelial cells. Additionally, it was demonstrated that activated canonical Wnt/β-catenin signaling in injured lung tissue regulated the myofibroblast differentiation of MSCs in vivo. The in vitro study results demonstrated that activation of the Wnt/β-catenin signaling stimulated MSCs to express myofibroblast markers; however, this process was attenuated by Wnt antagonist DKK1. Therefore, the results demonstrated that the aberrant activation of Wnt signaling induces the myofibroblast differentiation of engrafted MSCs, thus contributing to pulmonary fibrosis following lung injury. |
| doi_str_mv | 10.3892/ijmm.2014.1672 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4020487</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A437004796</galeid><sourcerecordid>A437004796</sourcerecordid><originalsourceid>FETCH-LOGICAL-c518t-e2363b01b50e4ab5cdded1cb06c894f49c8a88eb8f54e36b9751b58066b18a193</originalsourceid><addsrcrecordid>eNptks1rFDEYhwdRbK1ePUrAiwdnzeckcxGW4hcUvCh6C_ncZpkk6yRTWPznzdi6KpQcEpInD29-ebvuOYIbIkb8Juxj3GCI6AYNHD_ozhEfUY8p_f6wrRHkPeFsOOuelLKHEDM6isfdGaaME0bxefdza2q4UdVZ8C1VUMIuqSmkHQjJLsYVEI_ZBz1nPalSgQ3eu9mlGlQNOYHsQXTFJXN9jGoCpboIjJum8hqYnOoc9FJXW83gsEwxJzUfwW9fCeVp98irqbhnd_NF9_X9uy-XH_urzx8-XW6vesOQqL3DZCAaIs2go0ozY62zyGg4GDFST0cjlBBOC8-oI4MeOWusgMOgkVBoJBfd21vvYdHRWdPKn9UkD3OIrRyZVZD_n6RwLXf5RlKIIRW8CV7eCeb8Y3Glyn1e5hZUkU2PW5Icwr_UTk1OhuRzk5kYipFbShpB-Tg0anMP1YZ1MbTMnA9t_74LpoVWZudPhSMo1x6Qaw_ItQfk2gPtwot_n3vC_3x6A17dAuWgkg02lxOzqnpCesh6BEdOfgHZyL3y</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1932354700</pqid></control><display><type>article</type><title>Activated Wnt signaling induces myofibroblast differentiation of mesenchymal stem cells, contributing to pulmonary fibrosis</title><source>Spandidos Publications Journals</source><source>MEDLINE</source><source>Alma/SFX Local Collection</source><source>EZB Electronic Journals Library</source><creator>SUN, ZHAORUI ; WANG, CONG ; SHI, CHAOWEN ; SUN, FANGFANG ; XU, XIAOMENG ; QIAN, WEIPING ; NIE, SHINAN ; HAN, XIAODONG</creator><creatorcontrib>SUN, ZHAORUI ; WANG, CONG ; SHI, CHAOWEN ; SUN, FANGFANG ; XU, XIAOMENG ; QIAN, WEIPING ; NIE, SHINAN ; HAN, XIAODONG</creatorcontrib><description>Acute lung injury may lead to fibrogenesis. However, no treatment is currently available. This study was conducted to determine the effects of bone marrow-derived mesenchymal stem cells (MSCs) in a model of HCl-induced acute lung injury in Sprague-Dawley (SD) rats. Stromal cell-derived factor (SDF)-1 and its receptor CXC chemokine receptor (CXCR)4 have been shown to participate in mobilizing MSCs. Adenovirus carrying the CXCR4 gene was used to transfect MSCs in order to increase the engraftment numbers of MSCs at injured sites. Histological examination data demonstrated that the engraftment of MSCs did not attenuate lung injury and pulmonary fibrosis. The results showed that engraftment of MSCs almost differentiated into myofibroblasts, but rarely differentiated into lung epithelial cells. Additionally, it was demonstrated that activated canonical Wnt/β-catenin signaling in injured lung tissue regulated the myofibroblast differentiation of MSCs in vivo. The in vitro study results demonstrated that activation of the Wnt/β-catenin signaling stimulated MSCs to express myofibroblast markers; however, this process was attenuated by Wnt antagonist DKK1. Therefore, the results demonstrated that the aberrant activation of Wnt signaling induces the myofibroblast differentiation of engrafted MSCs, thus contributing to pulmonary fibrosis following lung injury.</description><identifier>ISSN: 1107-3756</identifier><identifier>EISSN: 1791-244X</identifier><identifier>DOI: 10.3892/ijmm.2014.1672</identifier><identifier>PMID: 24573542</identifier><language>eng</language><publisher>Greece: D.A. Spandidos</publisher><subject>Adenoviruses ; Animals ; Bone marrow ; Cell differentiation ; Cell Differentiation - drug effects ; Cellular signal transduction ; Chemokines ; Development and progression ; Fibroblasts ; Fibrosis ; Flow cytometry ; Genetic aspects ; Hydrochloric Acid - toxicity ; Lung diseases ; lung injury ; Male ; mesenchymal stem cells ; Mesenchymal Stromal Cells - cytology ; Mesenchymal Stromal Cells - drug effects ; Myofibroblasts - cytology ; Myofibroblasts - drug effects ; Observations ; Pathogenesis ; Pulmonary fibrosis ; Pulmonary Fibrosis - etiology ; Pulmonary Fibrosis - metabolism ; Rats ; Rats, Sprague-Dawley ; Signal Transduction - drug effects ; Stem cells ; stromal cell-derived factor-1/CXC chemokine receptor 4 ; Tumor necrosis factor-TNF ; Wnt Proteins - metabolism ; Wnt/β-catenin signaling</subject><ispartof>International journal of molecular medicine, 2014-05, Vol.33 (5), p.1097-1109</ispartof><rights>Copyright © 2014, Spandidos Publications</rights><rights>COPYRIGHT 2014 Spandidos Publications</rights><rights>Copyright Spandidos Publications UK Ltd. 2014</rights><rights>Copyright © 2014, Spandidos Publications 2014</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c518t-e2363b01b50e4ab5cdded1cb06c894f49c8a88eb8f54e36b9751b58066b18a193</citedby><cites>FETCH-LOGICAL-c518t-e2363b01b50e4ab5cdded1cb06c894f49c8a88eb8f54e36b9751b58066b18a193</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,5556,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24573542$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>SUN, ZHAORUI</creatorcontrib><creatorcontrib>WANG, CONG</creatorcontrib><creatorcontrib>SHI, CHAOWEN</creatorcontrib><creatorcontrib>SUN, FANGFANG</creatorcontrib><creatorcontrib>XU, XIAOMENG</creatorcontrib><creatorcontrib>QIAN, WEIPING</creatorcontrib><creatorcontrib>NIE, SHINAN</creatorcontrib><creatorcontrib>HAN, XIAODONG</creatorcontrib><title>Activated Wnt signaling induces myofibroblast differentiation of mesenchymal stem cells, contributing to pulmonary fibrosis</title><title>International journal of molecular medicine</title><addtitle>Int J Mol Med</addtitle><description>Acute lung injury may lead to fibrogenesis. However, no treatment is currently available. This study was conducted to determine the effects of bone marrow-derived mesenchymal stem cells (MSCs) in a model of HCl-induced acute lung injury in Sprague-Dawley (SD) rats. Stromal cell-derived factor (SDF)-1 and its receptor CXC chemokine receptor (CXCR)4 have been shown to participate in mobilizing MSCs. Adenovirus carrying the CXCR4 gene was used to transfect MSCs in order to increase the engraftment numbers of MSCs at injured sites. Histological examination data demonstrated that the engraftment of MSCs did not attenuate lung injury and pulmonary fibrosis. The results showed that engraftment of MSCs almost differentiated into myofibroblasts, but rarely differentiated into lung epithelial cells. Additionally, it was demonstrated that activated canonical Wnt/β-catenin signaling in injured lung tissue regulated the myofibroblast differentiation of MSCs in vivo. The in vitro study results demonstrated that activation of the Wnt/β-catenin signaling stimulated MSCs to express myofibroblast markers; however, this process was attenuated by Wnt antagonist DKK1. Therefore, the results demonstrated that the aberrant activation of Wnt signaling induces the myofibroblast differentiation of engrafted MSCs, thus contributing to pulmonary fibrosis following lung injury.</description><subject>Adenoviruses</subject><subject>Animals</subject><subject>Bone marrow</subject><subject>Cell differentiation</subject><subject>Cell Differentiation - drug effects</subject><subject>Cellular signal transduction</subject><subject>Chemokines</subject><subject>Development and progression</subject><subject>Fibroblasts</subject><subject>Fibrosis</subject><subject>Flow cytometry</subject><subject>Genetic aspects</subject><subject>Hydrochloric Acid - toxicity</subject><subject>Lung diseases</subject><subject>lung injury</subject><subject>Male</subject><subject>mesenchymal stem cells</subject><subject>Mesenchymal Stromal Cells - cytology</subject><subject>Mesenchymal Stromal Cells - drug effects</subject><subject>Myofibroblasts - cytology</subject><subject>Myofibroblasts - drug effects</subject><subject>Observations</subject><subject>Pathogenesis</subject><subject>Pulmonary fibrosis</subject><subject>Pulmonary Fibrosis - etiology</subject><subject>Pulmonary Fibrosis - metabolism</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Signal Transduction - drug effects</subject><subject>Stem cells</subject><subject>stromal cell-derived factor-1/CXC chemokine receptor 4</subject><subject>Tumor necrosis factor-TNF</subject><subject>Wnt Proteins - metabolism</subject><subject>Wnt/β-catenin signaling</subject><issn>1107-3756</issn><issn>1791-244X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNptks1rFDEYhwdRbK1ePUrAiwdnzeckcxGW4hcUvCh6C_ncZpkk6yRTWPznzdi6KpQcEpInD29-ebvuOYIbIkb8Juxj3GCI6AYNHD_ozhEfUY8p_f6wrRHkPeFsOOuelLKHEDM6isfdGaaME0bxefdza2q4UdVZ8C1VUMIuqSmkHQjJLsYVEI_ZBz1nPalSgQ3eu9mlGlQNOYHsQXTFJXN9jGoCpboIjJum8hqYnOoc9FJXW83gsEwxJzUfwW9fCeVp98irqbhnd_NF9_X9uy-XH_urzx8-XW6vesOQqL3DZCAaIs2go0ozY62zyGg4GDFST0cjlBBOC8-oI4MeOWusgMOgkVBoJBfd21vvYdHRWdPKn9UkD3OIrRyZVZD_n6RwLXf5RlKIIRW8CV7eCeb8Y3Glyn1e5hZUkU2PW5Icwr_UTk1OhuRzk5kYipFbShpB-Tg0anMP1YZ1MbTMnA9t_74LpoVWZudPhSMo1x6Qaw_ItQfk2gPtwot_n3vC_3x6A17dAuWgkg02lxOzqnpCesh6BEdOfgHZyL3y</recordid><startdate>20140501</startdate><enddate>20140501</enddate><creator>SUN, ZHAORUI</creator><creator>WANG, CONG</creator><creator>SHI, CHAOWEN</creator><creator>SUN, FANGFANG</creator><creator>XU, XIAOMENG</creator><creator>QIAN, WEIPING</creator><creator>NIE, SHINAN</creator><creator>HAN, XIAODONG</creator><general>D.A. Spandidos</general><general>Spandidos Publications</general><general>Spandidos Publications UK Ltd</general><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>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>5PM</scope></search><sort><creationdate>20140501</creationdate><title>Activated Wnt signaling induces myofibroblast differentiation of mesenchymal stem cells, contributing to pulmonary fibrosis</title><author>SUN, ZHAORUI ; WANG, CONG ; SHI, CHAOWEN ; SUN, FANGFANG ; XU, XIAOMENG ; QIAN, WEIPING ; NIE, SHINAN ; HAN, XIAODONG</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c518t-e2363b01b50e4ab5cdded1cb06c894f49c8a88eb8f54e36b9751b58066b18a193</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Adenoviruses</topic><topic>Animals</topic><topic>Bone marrow</topic><topic>Cell differentiation</topic><topic>Cell Differentiation - drug effects</topic><topic>Cellular signal transduction</topic><topic>Chemokines</topic><topic>Development and progression</topic><topic>Fibroblasts</topic><topic>Fibrosis</topic><topic>Flow cytometry</topic><topic>Genetic aspects</topic><topic>Hydrochloric Acid - toxicity</topic><topic>Lung diseases</topic><topic>lung injury</topic><topic>Male</topic><topic>mesenchymal stem cells</topic><topic>Mesenchymal Stromal Cells - cytology</topic><topic>Mesenchymal Stromal Cells - drug effects</topic><topic>Myofibroblasts - cytology</topic><topic>Myofibroblasts - drug effects</topic><topic>Observations</topic><topic>Pathogenesis</topic><topic>Pulmonary fibrosis</topic><topic>Pulmonary Fibrosis - etiology</topic><topic>Pulmonary Fibrosis - metabolism</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Signal Transduction - drug effects</topic><topic>Stem cells</topic><topic>stromal cell-derived factor-1/CXC chemokine receptor 4</topic><topic>Tumor necrosis factor-TNF</topic><topic>Wnt Proteins - metabolism</topic><topic>Wnt/β-catenin signaling</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>SUN, ZHAORUI</creatorcontrib><creatorcontrib>WANG, CONG</creatorcontrib><creatorcontrib>SHI, CHAOWEN</creatorcontrib><creatorcontrib>SUN, FANGFANG</creatorcontrib><creatorcontrib>XU, XIAOMENG</creatorcontrib><creatorcontrib>QIAN, WEIPING</creatorcontrib><creatorcontrib>NIE, SHINAN</creatorcontrib><creatorcontrib>HAN, XIAODONG</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>International journal of molecular medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>SUN, ZHAORUI</au><au>WANG, CONG</au><au>SHI, CHAOWEN</au><au>SUN, FANGFANG</au><au>XU, XIAOMENG</au><au>QIAN, WEIPING</au><au>NIE, SHINAN</au><au>HAN, XIAODONG</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Activated Wnt signaling induces myofibroblast differentiation of mesenchymal stem cells, contributing to pulmonary fibrosis</atitle><jtitle>International journal of molecular medicine</jtitle><addtitle>Int J Mol Med</addtitle><date>2014-05-01</date><risdate>2014</risdate><volume>33</volume><issue>5</issue><spage>1097</spage><epage>1109</epage><pages>1097-1109</pages><issn>1107-3756</issn><eissn>1791-244X</eissn><abstract>Acute lung injury may lead to fibrogenesis. However, no treatment is currently available. This study was conducted to determine the effects of bone marrow-derived mesenchymal stem cells (MSCs) in a model of HCl-induced acute lung injury in Sprague-Dawley (SD) rats. Stromal cell-derived factor (SDF)-1 and its receptor CXC chemokine receptor (CXCR)4 have been shown to participate in mobilizing MSCs. Adenovirus carrying the CXCR4 gene was used to transfect MSCs in order to increase the engraftment numbers of MSCs at injured sites. Histological examination data demonstrated that the engraftment of MSCs did not attenuate lung injury and pulmonary fibrosis. The results showed that engraftment of MSCs almost differentiated into myofibroblasts, but rarely differentiated into lung epithelial cells. Additionally, it was demonstrated that activated canonical Wnt/β-catenin signaling in injured lung tissue regulated the myofibroblast differentiation of MSCs in vivo. The in vitro study results demonstrated that activation of the Wnt/β-catenin signaling stimulated MSCs to express myofibroblast markers; however, this process was attenuated by Wnt antagonist DKK1. Therefore, the results demonstrated that the aberrant activation of Wnt signaling induces the myofibroblast differentiation of engrafted MSCs, thus contributing to pulmonary fibrosis following lung injury.</abstract><cop>Greece</cop><pub>D.A. Spandidos</pub><pmid>24573542</pmid><doi>10.3892/ijmm.2014.1672</doi><tpages>13</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1107-3756 |
| ispartof | International journal of molecular medicine, 2014-05, Vol.33 (5), p.1097-1109 |
| issn | 1107-3756 1791-244X |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4020487 |
| source | Spandidos Publications Journals; MEDLINE; Alma/SFX Local Collection; EZB Electronic Journals Library |
| subjects | Adenoviruses Animals Bone marrow Cell differentiation Cell Differentiation - drug effects Cellular signal transduction Chemokines Development and progression Fibroblasts Fibrosis Flow cytometry Genetic aspects Hydrochloric Acid - toxicity Lung diseases lung injury Male mesenchymal stem cells Mesenchymal Stromal Cells - cytology Mesenchymal Stromal Cells - drug effects Myofibroblasts - cytology Myofibroblasts - drug effects Observations Pathogenesis Pulmonary fibrosis Pulmonary Fibrosis - etiology Pulmonary Fibrosis - metabolism Rats Rats, Sprague-Dawley Signal Transduction - drug effects Stem cells stromal cell-derived factor-1/CXC chemokine receptor 4 Tumor necrosis factor-TNF Wnt Proteins - metabolism Wnt/β-catenin signaling |
| title | Activated Wnt signaling induces myofibroblast differentiation of mesenchymal stem cells, contributing to pulmonary fibrosis |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-11T17%3A20%3A37IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Activated%20Wnt%20signaling%20induces%20myofibroblast%20differentiation%20of%20mesenchymal%20stem%20cells,%20contributing%20to%20pulmonary%20fibrosis&rft.jtitle=International%20journal%20of%20molecular%20medicine&rft.au=SUN,%20ZHAORUI&rft.date=2014-05-01&rft.volume=33&rft.issue=5&rft.spage=1097&rft.epage=1109&rft.pages=1097-1109&rft.issn=1107-3756&rft.eissn=1791-244X&rft_id=info:doi/10.3892/ijmm.2014.1672&rft_dat=%3Cgale_pubme%3EA437004796%3C/gale_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1932354700&rft_id=info:pmid/24573542&rft_galeid=A437004796&rfr_iscdi=true |