Topical N-acetylcysteine accelerates wound healing in vitro and in vivo via the PKC/Stat3 pathway
N-Acetylcysteine (Nac) is an antioxidant administered in both oral and injectable forms. In this study, we used Nac topically to treat burn wounds in vitro and in vivo to investigate mechanisms of action. In vitro, we monitored glutathione levels, cell proliferation, migration, scratch-wound healing...
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| Veröffentlicht in: | International journal of molecular sciences 2014-05, Vol.15 (5), p.7563-7578 |
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| container_title | International journal of molecular sciences |
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| creator | Tsai, Min-Ling Huang, Hui-Pei Hsu, Jeng-Dong Lai, Yung-Rung Hsiao, Yu-Ping Lu, Fung-Jou Chang, Horng-Rong |
| description | N-Acetylcysteine (Nac) is an antioxidant administered in both oral and injectable forms. In this study, we used Nac topically to treat burn wounds in vitro and in vivo to investigate mechanisms of action. In vitro, we monitored glutathione levels, cell proliferation, migration, scratch-wound healing activities and the epithelialization-related proteins, matrixmetalloproteinase-1 (MMP-1) and proteins involved in regulating the expression of MMP-1 in CCD-966SK cells treated with Nac. Various Nac concentrations (0.1, 0.5, and 1.0 mM) increased glutathione levels, cell viability, scratch-wound healing activities and migration abilities of CCD-966SK cells in a dose-dependent manner. The MMP-1 expression of CCD-966SK cells treated with 1.0 mM Nac for 24 h was significantly increased. Levels of phosphatidylinositol 3-kinase (PI3K), protein kinase C (PKC), janus kinase 1 (Jak1), signal transducer and activator of transcription 3 (Stat3), c-Fos and Jun, but not extracellular signal-regulated protein kinases 1 and 2 (Erk1/2), were also significantly increased in a dose-dependent manner compared to the controls. In addition, Nac induced collagenous expression of MMP-1 via the PKC/Stat3 signaling pathway. In vivo, a burn wound healing rat model was applied to assess the stimulation activity and histopathological effects of Nac, with 3.0% Nac-treated wounds being found to show better characteristics on re-epithelialization. Our results demonstrated that Nac can potentially promote wound healing activity, and may be a promising drug to accelerate burn wound healing. |
| doi_str_mv | 10.3390/ijms15057563 |
| format | Article |
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In this study, we used Nac topically to treat burn wounds in vitro and in vivo to investigate mechanisms of action. In vitro, we monitored glutathione levels, cell proliferation, migration, scratch-wound healing activities and the epithelialization-related proteins, matrixmetalloproteinase-1 (MMP-1) and proteins involved in regulating the expression of MMP-1 in CCD-966SK cells treated with Nac. Various Nac concentrations (0.1, 0.5, and 1.0 mM) increased glutathione levels, cell viability, scratch-wound healing activities and migration abilities of CCD-966SK cells in a dose-dependent manner. The MMP-1 expression of CCD-966SK cells treated with 1.0 mM Nac for 24 h was significantly increased. Levels of phosphatidylinositol 3-kinase (PI3K), protein kinase C (PKC), janus kinase 1 (Jak1), signal transducer and activator of transcription 3 (Stat3), c-Fos and Jun, but not extracellular signal-regulated protein kinases 1 and 2 (Erk1/2), were also significantly increased in a dose-dependent manner compared to the controls. In addition, Nac induced collagenous expression of MMP-1 via the PKC/Stat3 signaling pathway. In vivo, a burn wound healing rat model was applied to assess the stimulation activity and histopathological effects of Nac, with 3.0% Nac-treated wounds being found to show better characteristics on re-epithelialization. Our results demonstrated that Nac can potentially promote wound healing activity, and may be a promising drug to accelerate burn wound healing.</description><identifier>ISSN: 1422-0067</identifier><identifier>ISSN: 1661-6596</identifier><identifier>EISSN: 1422-0067</identifier><identifier>DOI: 10.3390/ijms15057563</identifier><identifier>PMID: 24798751</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Acetylcysteine - administration & dosage ; Acetylcysteine - therapeutic use ; Administration, Topical ; Animals ; Antioxidants ; Antioxidants - administration & dosage ; Antioxidants - therapeutic use ; Burn treatment ; Burns - drug therapy ; Burns - metabolism ; Burns - pathology ; Cell Line ; Cell Proliferation - drug effects ; Cellular biology ; Humans ; Male ; Mitogen-Activated Protein Kinase 1 - metabolism ; Protein Kinase C - metabolism ; Rats ; Rats, Wistar ; Signal transduction ; Signal Transduction - drug effects ; Skin - drug effects ; Skin - metabolism ; Skin - pathology ; STAT3 Transcription Factor - metabolism ; Wound healing ; Wound Healing - drug effects</subject><ispartof>International journal of molecular sciences, 2014-05, Vol.15 (5), p.7563-7578</ispartof><rights>Copyright MDPI AG 2014</rights><rights>2014 by the authors; licensee MDPI, Basel, Switzerland 2014</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c478t-51cc364d4768405ed57f286627f1af387f2756138ddd4251f4e121a2f82588733</citedby><cites>FETCH-LOGICAL-c478t-51cc364d4768405ed57f286627f1af387f2756138ddd4251f4e121a2f82588733</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/PMC4057691/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4057691/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,725,778,782,883,27907,27908,53774,53776</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24798751$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Tsai, Min-Ling</creatorcontrib><creatorcontrib>Huang, Hui-Pei</creatorcontrib><creatorcontrib>Hsu, Jeng-Dong</creatorcontrib><creatorcontrib>Lai, Yung-Rung</creatorcontrib><creatorcontrib>Hsiao, Yu-Ping</creatorcontrib><creatorcontrib>Lu, Fung-Jou</creatorcontrib><creatorcontrib>Chang, Horng-Rong</creatorcontrib><title>Topical N-acetylcysteine accelerates wound healing in vitro and in vivo via the PKC/Stat3 pathway</title><title>International journal of molecular sciences</title><addtitle>Int J Mol Sci</addtitle><description>N-Acetylcysteine (Nac) is an antioxidant administered in both oral and injectable forms. In this study, we used Nac topically to treat burn wounds in vitro and in vivo to investigate mechanisms of action. In vitro, we monitored glutathione levels, cell proliferation, migration, scratch-wound healing activities and the epithelialization-related proteins, matrixmetalloproteinase-1 (MMP-1) and proteins involved in regulating the expression of MMP-1 in CCD-966SK cells treated with Nac. Various Nac concentrations (0.1, 0.5, and 1.0 mM) increased glutathione levels, cell viability, scratch-wound healing activities and migration abilities of CCD-966SK cells in a dose-dependent manner. The MMP-1 expression of CCD-966SK cells treated with 1.0 mM Nac for 24 h was significantly increased. Levels of phosphatidylinositol 3-kinase (PI3K), protein kinase C (PKC), janus kinase 1 (Jak1), signal transducer and activator of transcription 3 (Stat3), c-Fos and Jun, but not extracellular signal-regulated protein kinases 1 and 2 (Erk1/2), were also significantly increased in a dose-dependent manner compared to the controls. In addition, Nac induced collagenous expression of MMP-1 via the PKC/Stat3 signaling pathway. In vivo, a burn wound healing rat model was applied to assess the stimulation activity and histopathological effects of Nac, with 3.0% Nac-treated wounds being found to show better characteristics on re-epithelialization. Our results demonstrated that Nac can potentially promote wound healing activity, and may be a promising drug to accelerate burn wound healing.</description><subject>Acetylcysteine - administration & dosage</subject><subject>Acetylcysteine - therapeutic use</subject><subject>Administration, Topical</subject><subject>Animals</subject><subject>Antioxidants</subject><subject>Antioxidants - administration & dosage</subject><subject>Antioxidants - therapeutic use</subject><subject>Burn treatment</subject><subject>Burns - drug therapy</subject><subject>Burns - metabolism</subject><subject>Burns - pathology</subject><subject>Cell Line</subject><subject>Cell Proliferation - drug effects</subject><subject>Cellular biology</subject><subject>Humans</subject><subject>Male</subject><subject>Mitogen-Activated Protein Kinase 1 - metabolism</subject><subject>Protein Kinase C - metabolism</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Signal transduction</subject><subject>Signal Transduction - drug effects</subject><subject>Skin - drug effects</subject><subject>Skin - metabolism</subject><subject>Skin - pathology</subject><subject>STAT3 Transcription Factor - metabolism</subject><subject>Wound healing</subject><subject>Wound Healing - drug effects</subject><issn>1422-0067</issn><issn>1661-6596</issn><issn>1422-0067</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNpdkUtPGzEUha0KVB7truvKEpsuGPBz7NlUQlF5CASVmq6tW4-HOJqMU9uTKP8eQyhK2di-9qdz7_FB6AslZ5w35NzPF4lKIpWs-Qd0SAVjFSG12ts5H6CjlOaEMM5k8xEdMKEarSQ9RDANS2-hx_cVWJc3vd2k7PzgMFjrehchu4TXYRxaPHPQ--ER-wGvfI4BQ7l8KVahLIDzzOGft5PzXxkyx0vIszVsPqH9DvrkPr_ux-j35Y_p5Lq6e7i6mVzcVVYonStJreW1aIWqtSDStVJ1TNc1Ux2FjutSFYeU67ZtBZO0E44yCqzTTGqtOD9G37e6y_HPwrXWDTlCb5bRLyBuTABv_n8Z_Mw8hpUp3VTd0CLw7VUghr-jS9ksfCp_0MPgwpgMlYwWjEtd0JN36DyMcSj2DNWENrIW-nmi0y1lY0gpuu5tGErMc3ZmN7uCf9018Ab_C4s_Aa0alIM</recordid><startdate>20140502</startdate><enddate>20140502</enddate><creator>Tsai, Min-Ling</creator><creator>Huang, Hui-Pei</creator><creator>Hsu, Jeng-Dong</creator><creator>Lai, Yung-Rung</creator><creator>Hsiao, Yu-Ping</creator><creator>Lu, Fung-Jou</creator><creator>Chang, Horng-Rong</creator><general>MDPI AG</general><general>Molecular Diversity Preservation International (MDPI)</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>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>MBDVC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20140502</creationdate><title>Topical N-acetylcysteine accelerates wound healing in vitro and in vivo via the PKC/Stat3 pathway</title><author>Tsai, Min-Ling ; 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In this study, we used Nac topically to treat burn wounds in vitro and in vivo to investigate mechanisms of action. In vitro, we monitored glutathione levels, cell proliferation, migration, scratch-wound healing activities and the epithelialization-related proteins, matrixmetalloproteinase-1 (MMP-1) and proteins involved in regulating the expression of MMP-1 in CCD-966SK cells treated with Nac. Various Nac concentrations (0.1, 0.5, and 1.0 mM) increased glutathione levels, cell viability, scratch-wound healing activities and migration abilities of CCD-966SK cells in a dose-dependent manner. The MMP-1 expression of CCD-966SK cells treated with 1.0 mM Nac for 24 h was significantly increased. Levels of phosphatidylinositol 3-kinase (PI3K), protein kinase C (PKC), janus kinase 1 (Jak1), signal transducer and activator of transcription 3 (Stat3), c-Fos and Jun, but not extracellular signal-regulated protein kinases 1 and 2 (Erk1/2), were also significantly increased in a dose-dependent manner compared to the controls. In addition, Nac induced collagenous expression of MMP-1 via the PKC/Stat3 signaling pathway. In vivo, a burn wound healing rat model was applied to assess the stimulation activity and histopathological effects of Nac, with 3.0% Nac-treated wounds being found to show better characteristics on re-epithelialization. Our results demonstrated that Nac can potentially promote wound healing activity, and may be a promising drug to accelerate burn wound healing.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>24798751</pmid><doi>10.3390/ijms15057563</doi><tpages>16</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; MDPI - Multidisciplinary Digital Publishing Institute; PubMed Central |
| subjects | Acetylcysteine - administration & dosage Acetylcysteine - therapeutic use Administration, Topical Animals Antioxidants Antioxidants - administration & dosage Antioxidants - therapeutic use Burn treatment Burns - drug therapy Burns - metabolism Burns - pathology Cell Line Cell Proliferation - drug effects Cellular biology Humans Male Mitogen-Activated Protein Kinase 1 - metabolism Protein Kinase C - metabolism Rats Rats, Wistar Signal transduction Signal Transduction - drug effects Skin - drug effects Skin - metabolism Skin - pathology STAT3 Transcription Factor - metabolism Wound healing Wound Healing - drug effects |
| title | Topical N-acetylcysteine accelerates wound healing in vitro and in vivo via the PKC/Stat3 pathway |
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