Exosome production and its regulation of EGFR during wound healing in renal tubular cells
Kidney repair following injury involves the reconstitution of a structurally and functionally intact tubular epithelium. Growth factors and their receptors, such as EGFR, are important in the repair of renal tubules. Exosomes are cell-produced small (~100 nm in diameter) vesicles that contain and tr...
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| Veröffentlicht in: | American journal of physiology. Renal physiology 2017-06, Vol.312 (6), p.F963-F970 |
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| container_title | American journal of physiology. Renal physiology |
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| creator | Zhou, Xiangjun Zhang, Wei Yao, Qisheng Zhang, Hao Dong, Guie Zhang, Ming Liu, Yutao Chen, Jian-Kang Dong, Zheng |
| description | Kidney repair following injury involves the reconstitution of a structurally and functionally intact tubular epithelium. Growth factors and their receptors, such as EGFR, are important in the repair of renal tubules. Exosomes are cell-produced small (~100 nm in diameter) vesicles that contain and transfer proteins, lipids, RNAs, and DNAs between cells. In this study, we examined the relationship between exosome production and EGFR activation and the potential role of exosome in wound healing. EGFR activation occurred shortly after scratch wounding in renal tubular cells. Wound repair after scratching was significantly promoted by EGF and suppressed by EGFR inhibitor gefitinib. Interestingly, scratch wounding induced a significant increase of exosome production. The exosome production was decreased by EGF and increased by gefitinib, suggesting a suppressive role of EGFR signaling in exosome production. Conversely, inhibition of exosome release by GW4869 and manumycin A markedly increased EGFR activation and promoted wound healing. Moreover, exosomes derived from scratch-wounding cells could inhibit wound healing. Collectively, the results indicate that wound healing in renal tubular cells is associated with EGFR activation and exosome production. Although EGFR activation promotes wound healing, released exosomes may antagonize EGFR activation and wound healing. |
| doi_str_mv | 10.1152/ajprenal.00078.2017 |
| format | Article |
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Growth factors and their receptors, such as EGFR, are important in the repair of renal tubules. Exosomes are cell-produced small (~100 nm in diameter) vesicles that contain and transfer proteins, lipids, RNAs, and DNAs between cells. In this study, we examined the relationship between exosome production and EGFR activation and the potential role of exosome in wound healing. EGFR activation occurred shortly after scratch wounding in renal tubular cells. Wound repair after scratching was significantly promoted by EGF and suppressed by EGFR inhibitor gefitinib. Interestingly, scratch wounding induced a significant increase of exosome production. The exosome production was decreased by EGF and increased by gefitinib, suggesting a suppressive role of EGFR signaling in exosome production. Conversely, inhibition of exosome release by GW4869 and manumycin A markedly increased EGFR activation and promoted wound healing. Moreover, exosomes derived from scratch-wounding cells could inhibit wound healing. Collectively, the results indicate that wound healing in renal tubular cells is associated with EGFR activation and exosome production. Although EGFR activation promotes wound healing, released exosomes may antagonize EGFR activation and wound healing.</description><identifier>ISSN: 1931-857X</identifier><identifier>EISSN: 1522-1466</identifier><identifier>DOI: 10.1152/ajprenal.00078.2017</identifier><identifier>PMID: 28356285</identifier><language>eng</language><publisher>United States: American Physiological Society</publisher><subject>Aniline Compounds - pharmacology ; Animals ; Benzylidene Compounds - pharmacology ; Cell Line ; Cells ; Epidermal growth factor ; Epidermal Growth Factor - pharmacology ; Epidermal growth factor receptors ; Epithelial Cells - drug effects ; Epithelial Cells - metabolism ; Epithelial Cells - pathology ; Epithelium ; ErbB Receptors - antagonists & inhibitors ; ErbB Receptors - metabolism ; Exosomes ; Exosomes - metabolism ; Exosomes - pathology ; Gefitinib ; Growth factors ; Kidney Tubules - drug effects ; Kidney Tubules - metabolism ; Kidney Tubules - pathology ; Kidneys ; Lipids ; Mice ; Polyenes - pharmacology ; Polyunsaturated Alkamides - pharmacology ; Proteins ; Quinazolines - pharmacology ; Renal tubules ; Ribonucleic acid ; RNA ; Signal Transduction ; Time Factors ; Wound healing ; Wound Healing - drug effects</subject><ispartof>American journal of physiology. Renal physiology, 2017-06, Vol.312 (6), p.F963-F970</ispartof><rights>Copyright © 2017 the American Physiological Society.</rights><rights>Copyright American Physiological Society Jun 2017</rights><rights>Copyright © 2017 the American Physiological Society 2017 American Physiological Society</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c433t-404360fbe1351e5164507a22b095a3f04fba95c91aded877e438da0255cf507e3</citedby><cites>FETCH-LOGICAL-c433t-404360fbe1351e5164507a22b095a3f04fba95c91aded877e438da0255cf507e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,3039,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28356285$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhou, Xiangjun</creatorcontrib><creatorcontrib>Zhang, Wei</creatorcontrib><creatorcontrib>Yao, Qisheng</creatorcontrib><creatorcontrib>Zhang, Hao</creatorcontrib><creatorcontrib>Dong, Guie</creatorcontrib><creatorcontrib>Zhang, Ming</creatorcontrib><creatorcontrib>Liu, Yutao</creatorcontrib><creatorcontrib>Chen, Jian-Kang</creatorcontrib><creatorcontrib>Dong, Zheng</creatorcontrib><title>Exosome production and its regulation of EGFR during wound healing in renal tubular cells</title><title>American journal of physiology. Renal physiology</title><addtitle>Am J Physiol Renal Physiol</addtitle><description>Kidney repair following injury involves the reconstitution of a structurally and functionally intact tubular epithelium. Growth factors and their receptors, such as EGFR, are important in the repair of renal tubules. Exosomes are cell-produced small (~100 nm in diameter) vesicles that contain and transfer proteins, lipids, RNAs, and DNAs between cells. In this study, we examined the relationship between exosome production and EGFR activation and the potential role of exosome in wound healing. EGFR activation occurred shortly after scratch wounding in renal tubular cells. Wound repair after scratching was significantly promoted by EGF and suppressed by EGFR inhibitor gefitinib. Interestingly, scratch wounding induced a significant increase of exosome production. The exosome production was decreased by EGF and increased by gefitinib, suggesting a suppressive role of EGFR signaling in exosome production. Conversely, inhibition of exosome release by GW4869 and manumycin A markedly increased EGFR activation and promoted wound healing. Moreover, exosomes derived from scratch-wounding cells could inhibit wound healing. Collectively, the results indicate that wound healing in renal tubular cells is associated with EGFR activation and exosome production. Although EGFR activation promotes wound healing, released exosomes may antagonize EGFR activation and wound healing.</description><subject>Aniline Compounds - pharmacology</subject><subject>Animals</subject><subject>Benzylidene Compounds - pharmacology</subject><subject>Cell Line</subject><subject>Cells</subject><subject>Epidermal growth factor</subject><subject>Epidermal Growth Factor - pharmacology</subject><subject>Epidermal growth factor receptors</subject><subject>Epithelial Cells - drug effects</subject><subject>Epithelial Cells - metabolism</subject><subject>Epithelial Cells - pathology</subject><subject>Epithelium</subject><subject>ErbB Receptors - antagonists & inhibitors</subject><subject>ErbB Receptors - metabolism</subject><subject>Exosomes</subject><subject>Exosomes - metabolism</subject><subject>Exosomes - pathology</subject><subject>Gefitinib</subject><subject>Growth factors</subject><subject>Kidney Tubules - drug effects</subject><subject>Kidney Tubules - metabolism</subject><subject>Kidney Tubules - pathology</subject><subject>Kidneys</subject><subject>Lipids</subject><subject>Mice</subject><subject>Polyenes - pharmacology</subject><subject>Polyunsaturated Alkamides - pharmacology</subject><subject>Proteins</subject><subject>Quinazolines - pharmacology</subject><subject>Renal tubules</subject><subject>Ribonucleic acid</subject><subject>RNA</subject><subject>Signal Transduction</subject><subject>Time Factors</subject><subject>Wound healing</subject><subject>Wound Healing - drug effects</subject><issn>1931-857X</issn><issn>1522-1466</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkVtLxDAQhYMo3n-BIAFffOmaSZo2fRFkWS-wIIiCPoW0TdcubVOTxsu_N3sTFQLJZL4zzOEgdAJkBMDphZr3VneqGRFCUjGiBNIttB86NII4SbbDO2MQCZ4-76ED5-aBA6Cwi_aoYDyhgu-jl8mncabVuLem9MVQmw6rrsT14LDVM9-o5Zep8OTm-gGX3tbdDH8YH5hXrZpFVXd4uQgefB4EFhe6adwR2qlU4_Tx-j5ET9eTx_FtNL2_uRtfTaMiZmyIYhKzhFS5BsZBc0hiTlJFaU4yrlhF4ipXGS8yUKUuRZrqmIlSEcp5UQVSs0N0uZrb-7zVZaG7wapG9rZulf2SRtXyb6erX-XMvEseZ1yILAw4Xw-w5s1rN8i2dgsLqtPGOwlCUE4gnICe_UPnxttgPVAZpyQDECxQbEUV1jhndfWzDBC5iE5uopPL6OQiuqA6_e3jR7PJin0DJ5iXgw</recordid><startdate>20170601</startdate><enddate>20170601</enddate><creator>Zhou, Xiangjun</creator><creator>Zhang, Wei</creator><creator>Yao, Qisheng</creator><creator>Zhang, Hao</creator><creator>Dong, Guie</creator><creator>Zhang, Ming</creator><creator>Liu, Yutao</creator><creator>Chen, Jian-Kang</creator><creator>Dong, Zheng</creator><general>American Physiological Society</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><scope>5PM</scope></search><sort><creationdate>20170601</creationdate><title>Exosome production and its regulation of EGFR during wound healing in renal tubular cells</title><author>Zhou, Xiangjun ; Zhang, Wei ; Yao, Qisheng ; Zhang, Hao ; Dong, Guie ; Zhang, Ming ; Liu, Yutao ; Chen, Jian-Kang ; Dong, Zheng</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c433t-404360fbe1351e5164507a22b095a3f04fba95c91aded877e438da0255cf507e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Aniline Compounds - pharmacology</topic><topic>Animals</topic><topic>Benzylidene Compounds - pharmacology</topic><topic>Cell Line</topic><topic>Cells</topic><topic>Epidermal growth factor</topic><topic>Epidermal Growth Factor - pharmacology</topic><topic>Epidermal growth factor receptors</topic><topic>Epithelial Cells - drug effects</topic><topic>Epithelial Cells - metabolism</topic><topic>Epithelial Cells - pathology</topic><topic>Epithelium</topic><topic>ErbB Receptors - antagonists & inhibitors</topic><topic>ErbB Receptors - metabolism</topic><topic>Exosomes</topic><topic>Exosomes - metabolism</topic><topic>Exosomes - pathology</topic><topic>Gefitinib</topic><topic>Growth factors</topic><topic>Kidney Tubules - drug effects</topic><topic>Kidney Tubules - metabolism</topic><topic>Kidney Tubules - pathology</topic><topic>Kidneys</topic><topic>Lipids</topic><topic>Mice</topic><topic>Polyenes - pharmacology</topic><topic>Polyunsaturated Alkamides - pharmacology</topic><topic>Proteins</topic><topic>Quinazolines - pharmacology</topic><topic>Renal tubules</topic><topic>Ribonucleic acid</topic><topic>RNA</topic><topic>Signal Transduction</topic><topic>Time Factors</topic><topic>Wound healing</topic><topic>Wound Healing - drug effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhou, Xiangjun</creatorcontrib><creatorcontrib>Zhang, Wei</creatorcontrib><creatorcontrib>Yao, Qisheng</creatorcontrib><creatorcontrib>Zhang, Hao</creatorcontrib><creatorcontrib>Dong, Guie</creatorcontrib><creatorcontrib>Zhang, Ming</creatorcontrib><creatorcontrib>Liu, Yutao</creatorcontrib><creatorcontrib>Chen, Jian-Kang</creatorcontrib><creatorcontrib>Dong, Zheng</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><collection>PubMed Central (Full Participant titles)</collection><jtitle>American journal of physiology. Renal physiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhou, Xiangjun</au><au>Zhang, Wei</au><au>Yao, Qisheng</au><au>Zhang, Hao</au><au>Dong, Guie</au><au>Zhang, Ming</au><au>Liu, Yutao</au><au>Chen, Jian-Kang</au><au>Dong, Zheng</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Exosome production and its regulation of EGFR during wound healing in renal tubular cells</atitle><jtitle>American journal of physiology. Renal physiology</jtitle><addtitle>Am J Physiol Renal Physiol</addtitle><date>2017-06-01</date><risdate>2017</risdate><volume>312</volume><issue>6</issue><spage>F963</spage><epage>F970</epage><pages>F963-F970</pages><issn>1931-857X</issn><eissn>1522-1466</eissn><abstract>Kidney repair following injury involves the reconstitution of a structurally and functionally intact tubular epithelium. Growth factors and their receptors, such as EGFR, are important in the repair of renal tubules. Exosomes are cell-produced small (~100 nm in diameter) vesicles that contain and transfer proteins, lipids, RNAs, and DNAs between cells. In this study, we examined the relationship between exosome production and EGFR activation and the potential role of exosome in wound healing. EGFR activation occurred shortly after scratch wounding in renal tubular cells. Wound repair after scratching was significantly promoted by EGF and suppressed by EGFR inhibitor gefitinib. Interestingly, scratch wounding induced a significant increase of exosome production. The exosome production was decreased by EGF and increased by gefitinib, suggesting a suppressive role of EGFR signaling in exosome production. Conversely, inhibition of exosome release by GW4869 and manumycin A markedly increased EGFR activation and promoted wound healing. Moreover, exosomes derived from scratch-wounding cells could inhibit wound healing. Collectively, the results indicate that wound healing in renal tubular cells is associated with EGFR activation and exosome production. Although EGFR activation promotes wound healing, released exosomes may antagonize EGFR activation and wound healing.</abstract><cop>United States</cop><pub>American Physiological Society</pub><pmid>28356285</pmid><doi>10.1152/ajprenal.00078.2017</doi><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; American Physiological Society; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Aniline Compounds - pharmacology Animals Benzylidene Compounds - pharmacology Cell Line Cells Epidermal growth factor Epidermal Growth Factor - pharmacology Epidermal growth factor receptors Epithelial Cells - drug effects Epithelial Cells - metabolism Epithelial Cells - pathology Epithelium ErbB Receptors - antagonists & inhibitors ErbB Receptors - metabolism Exosomes Exosomes - metabolism Exosomes - pathology Gefitinib Growth factors Kidney Tubules - drug effects Kidney Tubules - metabolism Kidney Tubules - pathology Kidneys Lipids Mice Polyenes - pharmacology Polyunsaturated Alkamides - pharmacology Proteins Quinazolines - pharmacology Renal tubules Ribonucleic acid RNA Signal Transduction Time Factors Wound healing Wound Healing - drug effects |
| title | Exosome production and its regulation of EGFR during wound healing in renal tubular cells |
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