Heparin-binding EGF-like growth factor (HB-EGF) promotes cell migration and adhesion via focal adhesion kinase

Abstract Background Cell migration and adhesion are essential in intestinal epithelial wound healing and recovery from injury. Focal adhesion kinase (FAK) plays an important role in cell–extracellular matrix signal transduction. We have previously shown that heparin-binding EGF-like growth factor (H...

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Veröffentlicht in:The Journal of surgical research 2014-06, Vol.189 (2), p.222-231
Hauptverfasser: Su, Yanwei, MD, Besner, Gail E., MD
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Besner, Gail E., MD
description Abstract Background Cell migration and adhesion are essential in intestinal epithelial wound healing and recovery from injury. Focal adhesion kinase (FAK) plays an important role in cell–extracellular matrix signal transduction. We have previously shown that heparin-binding EGF-like growth factor (HB-EGF) promotes intestinal epithelial cell (IEC) migration and adhesion in vitro . The present study was designed to determine whether FAK is involved in HB-EGF–induced IEC migration and adhesion. Materials and methods A scrape wound healing model of rat IECs was used to examine the effect of HB-EGF on FAK-dependent cell migration in vitro . Immunofluorescence and Western blot analyses were performed to evaluate the effect of HB-EGF on the expression of phosphorylated FAK (p-FAK). Cell adhesion assays were performed to determine the role of FAK in HB-EGF–induced cell adhesion on fibronectin (FN). Results HB-EGF significantly increased healing after scrape wounding, an effect that was reversed in the presence of an FAK inhibitor 14 (both with P  
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Focal adhesion kinase (FAK) plays an important role in cell–extracellular matrix signal transduction. We have previously shown that heparin-binding EGF-like growth factor (HB-EGF) promotes intestinal epithelial cell (IEC) migration and adhesion in vitro . The present study was designed to determine whether FAK is involved in HB-EGF–induced IEC migration and adhesion. Materials and methods A scrape wound healing model of rat IECs was used to examine the effect of HB-EGF on FAK-dependent cell migration in vitro . Immunofluorescence and Western blot analyses were performed to evaluate the effect of HB-EGF on the expression of phosphorylated FAK (p-FAK). Cell adhesion assays were performed to determine the role of FAK in HB-EGF–induced cell adhesion on fibronectin (FN). Results HB-EGF significantly increased healing after scrape wounding, an effect that was reversed in the presence of an FAK inhibitor 14 (both with P  &lt; 0.05). HB-EGF increased p-FAK expression and induced p-FAK redistribution and actin reorganization in migrating rat IECs. Cell adhesion and spreading on FN were significantly increased by HB-EGF ( P  &lt; 0.05). FAK inhibitor 14 significantly inhibited both intrinsic and HB-EGF–induced cell adhesion and spreading on FN (both with P  &lt; 0.05). Conclusions FAK phosphorylation and FAK-mediated signal transduction play essential roles in HB-EGF–mediated IEC migration and adhesion.</description><identifier>ISSN: 0022-4804</identifier><identifier>EISSN: 1095-8673</identifier><identifier>DOI: 10.1016/j.jss.2014.02.055</identifier><identifier>PMID: 24703506</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Animals ; Cell Adhesion ; Cell Line ; Cell migration ; Cell Movement ; Epithelial Cells - physiology ; Fibronectins ; Focal adhesion kinase ; Focal Adhesion Protein-Tyrosine Kinases - physiology ; HB-EGF ; Heparin-binding EGF-like Growth Factor ; Intercellular Signaling Peptides and Proteins - physiology ; Intestinal Mucosa - enzymology ; Rats ; Surgery ; Wound Healing</subject><ispartof>The Journal of surgical research, 2014-06, Vol.189 (2), p.222-231</ispartof><rights>Elsevier Inc.</rights><rights>2014 Elsevier Inc.</rights><rights>Copyright © 2014 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c451t-36b482912c8185f73ef052513ec07c846af45340ac1a8e6c6cb4f270c18b2f593</citedby><cites>FETCH-LOGICAL-c451t-36b482912c8185f73ef052513ec07c846af45340ac1a8e6c6cb4f270c18b2f593</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.jss.2014.02.055$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24703506$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Su, Yanwei, MD</creatorcontrib><creatorcontrib>Besner, Gail E., MD</creatorcontrib><title>Heparin-binding EGF-like growth factor (HB-EGF) promotes cell migration and adhesion via focal adhesion kinase</title><title>The Journal of surgical research</title><addtitle>J Surg Res</addtitle><description>Abstract Background Cell migration and adhesion are essential in intestinal epithelial wound healing and recovery from injury. Focal adhesion kinase (FAK) plays an important role in cell–extracellular matrix signal transduction. We have previously shown that heparin-binding EGF-like growth factor (HB-EGF) promotes intestinal epithelial cell (IEC) migration and adhesion in vitro . The present study was designed to determine whether FAK is involved in HB-EGF–induced IEC migration and adhesion. Materials and methods A scrape wound healing model of rat IECs was used to examine the effect of HB-EGF on FAK-dependent cell migration in vitro . Immunofluorescence and Western blot analyses were performed to evaluate the effect of HB-EGF on the expression of phosphorylated FAK (p-FAK). Cell adhesion assays were performed to determine the role of FAK in HB-EGF–induced cell adhesion on fibronectin (FN). Results HB-EGF significantly increased healing after scrape wounding, an effect that was reversed in the presence of an FAK inhibitor 14 (both with P  &lt; 0.05). HB-EGF increased p-FAK expression and induced p-FAK redistribution and actin reorganization in migrating rat IECs. Cell adhesion and spreading on FN were significantly increased by HB-EGF ( P  &lt; 0.05). FAK inhibitor 14 significantly inhibited both intrinsic and HB-EGF–induced cell adhesion and spreading on FN (both with P  &lt; 0.05). Conclusions FAK phosphorylation and FAK-mediated signal transduction play essential roles in HB-EGF–mediated IEC migration and adhesion.</description><subject>Animals</subject><subject>Cell Adhesion</subject><subject>Cell Line</subject><subject>Cell migration</subject><subject>Cell Movement</subject><subject>Epithelial Cells - physiology</subject><subject>Fibronectins</subject><subject>Focal adhesion kinase</subject><subject>Focal Adhesion Protein-Tyrosine Kinases - physiology</subject><subject>HB-EGF</subject><subject>Heparin-binding EGF-like Growth Factor</subject><subject>Intercellular Signaling Peptides and Proteins - physiology</subject><subject>Intestinal Mucosa - enzymology</subject><subject>Rats</subject><subject>Surgery</subject><subject>Wound Healing</subject><issn>0022-4804</issn><issn>1095-8673</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kUFv1DAQhS0EokvhB3BBPpZDgsexHa-QkKBqu0iVOABny3EmW2ez9mJni_rvcbQFJA6c7Bm_9zT-hpDXwGpgoN6N9ZhzzRmImvGaSfmErICtZaVV2zwlK8Y4r4Rm4oy8yHlkpV63zXNyxkXLGsnUioQNHmzyoep86H3Y0qub62ryO6TbFH_Od3Swbo6JXmw-VeXpLT2kuI8zZupwmujeb5OdfQzUhp7a_g7zUtx7S4fo7PS3tfPBZnxJng12yvjq8Twn36-vvl1uqtsvN58vP95WTkiYq0Z1QvM1cKdBy6FtcGCSS2jQsdZpoewgZCOYdWA1KqdcJwbeMge644NcN-fk4pRbxv1xxDybvc_LxDZgPGYDkivgWmkoUjhJXYo5JxzMIfm9TQ8GmFkwm9EUzGbBbBg3BXPxvHmMP3Z77P84fnMtgvcnAZZP3ntMJjuPwWHvE7rZ9NH_N_7DP243-eALzx0-YB7jMYVCz4DJxWC-Lnte1gxiuSlofgEnOaEj</recordid><startdate>20140615</startdate><enddate>20140615</enddate><creator>Su, Yanwei, MD</creator><creator>Besner, Gail E., MD</creator><general>Elsevier Inc</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>7X8</scope></search><sort><creationdate>20140615</creationdate><title>Heparin-binding EGF-like growth factor (HB-EGF) promotes cell migration and adhesion via focal adhesion kinase</title><author>Su, Yanwei, MD ; Besner, Gail E., MD</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c451t-36b482912c8185f73ef052513ec07c846af45340ac1a8e6c6cb4f270c18b2f593</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Animals</topic><topic>Cell Adhesion</topic><topic>Cell Line</topic><topic>Cell migration</topic><topic>Cell Movement</topic><topic>Epithelial Cells - physiology</topic><topic>Fibronectins</topic><topic>Focal adhesion kinase</topic><topic>Focal Adhesion Protein-Tyrosine Kinases - physiology</topic><topic>HB-EGF</topic><topic>Heparin-binding EGF-like Growth Factor</topic><topic>Intercellular Signaling Peptides and Proteins - physiology</topic><topic>Intestinal Mucosa - enzymology</topic><topic>Rats</topic><topic>Surgery</topic><topic>Wound Healing</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Su, Yanwei, MD</creatorcontrib><creatorcontrib>Besner, Gail E., MD</creatorcontrib><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><jtitle>The Journal of surgical research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Su, Yanwei, MD</au><au>Besner, Gail E., MD</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Heparin-binding EGF-like growth factor (HB-EGF) promotes cell migration and adhesion via focal adhesion kinase</atitle><jtitle>The Journal of surgical research</jtitle><addtitle>J Surg Res</addtitle><date>2014-06-15</date><risdate>2014</risdate><volume>189</volume><issue>2</issue><spage>222</spage><epage>231</epage><pages>222-231</pages><issn>0022-4804</issn><eissn>1095-8673</eissn><abstract>Abstract Background Cell migration and adhesion are essential in intestinal epithelial wound healing and recovery from injury. Focal adhesion kinase (FAK) plays an important role in cell–extracellular matrix signal transduction. We have previously shown that heparin-binding EGF-like growth factor (HB-EGF) promotes intestinal epithelial cell (IEC) migration and adhesion in vitro . The present study was designed to determine whether FAK is involved in HB-EGF–induced IEC migration and adhesion. Materials and methods A scrape wound healing model of rat IECs was used to examine the effect of HB-EGF on FAK-dependent cell migration in vitro . Immunofluorescence and Western blot analyses were performed to evaluate the effect of HB-EGF on the expression of phosphorylated FAK (p-FAK). Cell adhesion assays were performed to determine the role of FAK in HB-EGF–induced cell adhesion on fibronectin (FN). Results HB-EGF significantly increased healing after scrape wounding, an effect that was reversed in the presence of an FAK inhibitor 14 (both with P  &lt; 0.05). HB-EGF increased p-FAK expression and induced p-FAK redistribution and actin reorganization in migrating rat IECs. Cell adhesion and spreading on FN were significantly increased by HB-EGF ( P  &lt; 0.05). FAK inhibitor 14 significantly inhibited both intrinsic and HB-EGF–induced cell adhesion and spreading on FN (both with P  &lt; 0.05). Conclusions FAK phosphorylation and FAK-mediated signal transduction play essential roles in HB-EGF–mediated IEC migration and adhesion.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>24703506</pmid><doi>10.1016/j.jss.2014.02.055</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record>
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subjects Animals
Cell Adhesion
Cell Line
Cell migration
Cell Movement
Epithelial Cells - physiology
Fibronectins
Focal adhesion kinase
Focal Adhesion Protein-Tyrosine Kinases - physiology
HB-EGF
Heparin-binding EGF-like Growth Factor
Intercellular Signaling Peptides and Proteins - physiology
Intestinal Mucosa - enzymology
Rats
Surgery
Wound Healing
title Heparin-binding EGF-like growth factor (HB-EGF) promotes cell migration and adhesion via focal adhesion kinase
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