Cytochrome P450 (CYP) epoxygenases as potential targets in the management of impaired diabetic wound healing
Epoxyeicosatrienoic acids (EETs) are the epoxidation products of arachidonic acid catalyzed by cytochrome P450 (CYP) epoxygenases, which possess multiple biological activities. In the present study, we aimed to explore the role and effects of CYP epoxygenases/EETs in wound healing in ob/ob mice. Ful...
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| Veröffentlicht in: | Laboratory investigation 2017-07, Vol.97 (7), p.782-791 |
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| creator | Zhao, Huichen Chen, Jicui Chai, Jiachao Zhang, Yuchao Yu, Cong Pan, Zhe Gao, Peng Zong, Chen Guan, Qingbo Fu, Yuqin Liu, Yuantao |
| description | Epoxyeicosatrienoic acids (EETs) are the epoxidation products of arachidonic acid catalyzed by cytochrome P450 (CYP) epoxygenases, which possess multiple biological activities. In the present study, we aimed to explore the role and effects of CYP epoxygenases/EETs in wound healing in ob/ob mice. Full-thickness skin dorsal wounds were made on ob/ob mice and C57BL/6 control mice. The mRNA and protein expression of CYP epoxygenases were determined in granulation tissues of wounds. Effects of EETs on wound healing were evaluated. Inflammation and angiogenesis in wounds were also observed. Compared with C57BL/6 mice, the mRNA and protein expression of CYP2C65 and CYP2J6 in the granulation tissues in ob/ob mice were significantly reduced. 11,12-EET treatment significantly improved wound healing in ob/ob mice, whereas 14,15-EEZE, an EET antagonist, showed the opposite effect. 11,12-EET treatment decreased neutrophil and macrophage infiltration to the wound sites, resulting in reduced production of inflammatory cytokines, decreased MMP-9 expression, and increased collagen accumulation in the granulation tissues of ob/ob mice. In addition, 11,12-EET increased angiogenesis in the granulation tissues of wounds in ob/ob mice. These findings indicate that reduced expression of CYP epoxygenases may contribute to impaired diabetic wound healing, and exogenous EETs may improve diabetic wound healing by modulating inflammation and angiogenesis. |
| doi_str_mv | 10.1038/labinvest.2017.21 |
| format | Article |
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In the present study, we aimed to explore the role and effects of CYP epoxygenases/EETs in wound healing in ob/ob mice. Full-thickness skin dorsal wounds were made on ob/ob mice and C57BL/6 control mice. The mRNA and protein expression of CYP epoxygenases were determined in granulation tissues of wounds. Effects of EETs on wound healing were evaluated. Inflammation and angiogenesis in wounds were also observed. Compared with C57BL/6 mice, the mRNA and protein expression of CYP2C65 and CYP2J6 in the granulation tissues in ob/ob mice were significantly reduced. 11,12-EET treatment significantly improved wound healing in ob/ob mice, whereas 14,15-EEZE, an EET antagonist, showed the opposite effect. 11,12-EET treatment decreased neutrophil and macrophage infiltration to the wound sites, resulting in reduced production of inflammatory cytokines, decreased MMP-9 expression, and increased collagen accumulation in the granulation tissues of ob/ob mice. In addition, 11,12-EET increased angiogenesis in the granulation tissues of wounds in ob/ob mice. These findings indicate that reduced expression of CYP epoxygenases may contribute to impaired diabetic wound healing, and exogenous EETs may improve diabetic wound healing by modulating inflammation and angiogenesis.</description><identifier>ISSN: 0023-6837</identifier><identifier>EISSN: 1530-0307</identifier><identifier>DOI: 10.1038/labinvest.2017.21</identifier><identifier>PMID: 28319086</identifier><language>eng</language><publisher>New York: Nature Publishing Group US</publisher><subject>631/337/2265 ; 64/60 ; 692/163/2743/137/138 ; 8,11,14-Eicosatrienoic Acid - analogs & derivatives ; 8,11,14-Eicosatrienoic Acid - pharmacology ; 82/51 ; 82/80 ; 96/1 ; Angiogenesis ; Animal models ; Animals ; Arachidonic acid ; Collagen ; Cytochrome ; Cytochrome P-450 CYP2J2 ; Cytochrome P-450 Enzyme System - drug effects ; Cytochrome P-450 Enzyme System - genetics ; Cytochrome P-450 Enzyme System - metabolism ; Cytochrome P450 ; Cytokines ; Cytokines - analysis ; Cytokines - metabolism ; Diabetes ; Diabetes Complications - metabolism ; Diabetes mellitus ; Epoxidation ; Gelatinase B ; Gene expression ; Granulation ; Infiltration ; Inflammation ; Laboratory Medicine ; Macrophages ; Medicine ; Medicine & Public Health ; Mice ; Mice, Inbred C57BL ; Mice, Obese ; mRNA ; Pathology ; Protein expression ; research-article ; Rodents ; Skin ; Skin Ulcer - metabolism ; Tissues ; Wound healing ; Wound Healing - drug effects</subject><ispartof>Laboratory investigation, 2017-07, Vol.97 (7), p.782-791</ispartof><rights>United States & Canadian Academy of Pathology USCAP, Inc 2017</rights><rights>Copyright Nature Publishing Group Jul 2017</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-p179t-da5964a979e620bc01215a48213b189e885887b9c5343c33fa176b3a8832e51f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28319086$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhao, Huichen</creatorcontrib><creatorcontrib>Chen, Jicui</creatorcontrib><creatorcontrib>Chai, Jiachao</creatorcontrib><creatorcontrib>Zhang, Yuchao</creatorcontrib><creatorcontrib>Yu, Cong</creatorcontrib><creatorcontrib>Pan, Zhe</creatorcontrib><creatorcontrib>Gao, Peng</creatorcontrib><creatorcontrib>Zong, Chen</creatorcontrib><creatorcontrib>Guan, Qingbo</creatorcontrib><creatorcontrib>Fu, Yuqin</creatorcontrib><creatorcontrib>Liu, Yuantao</creatorcontrib><title>Cytochrome P450 (CYP) epoxygenases as potential targets in the management of impaired diabetic wound healing</title><title>Laboratory investigation</title><addtitle>Lab Invest</addtitle><addtitle>Lab Invest</addtitle><description>Epoxyeicosatrienoic acids (EETs) are the epoxidation products of arachidonic acid catalyzed by cytochrome P450 (CYP) epoxygenases, which possess multiple biological activities. In the present study, we aimed to explore the role and effects of CYP epoxygenases/EETs in wound healing in ob/ob mice. Full-thickness skin dorsal wounds were made on ob/ob mice and C57BL/6 control mice. The mRNA and protein expression of CYP epoxygenases were determined in granulation tissues of wounds. Effects of EETs on wound healing were evaluated. Inflammation and angiogenesis in wounds were also observed. Compared with C57BL/6 mice, the mRNA and protein expression of CYP2C65 and CYP2J6 in the granulation tissues in ob/ob mice were significantly reduced. 11,12-EET treatment significantly improved wound healing in ob/ob mice, whereas 14,15-EEZE, an EET antagonist, showed the opposite effect. 11,12-EET treatment decreased neutrophil and macrophage infiltration to the wound sites, resulting in reduced production of inflammatory cytokines, decreased MMP-9 expression, and increased collagen accumulation in the granulation tissues of ob/ob mice. In addition, 11,12-EET increased angiogenesis in the granulation tissues of wounds in ob/ob mice. These findings indicate that reduced expression of CYP epoxygenases may contribute to impaired diabetic wound healing, and exogenous EETs may improve diabetic wound healing by modulating inflammation and angiogenesis.</description><subject>631/337/2265</subject><subject>64/60</subject><subject>692/163/2743/137/138</subject><subject>8,11,14-Eicosatrienoic Acid - analogs & derivatives</subject><subject>8,11,14-Eicosatrienoic Acid - pharmacology</subject><subject>82/51</subject><subject>82/80</subject><subject>96/1</subject><subject>Angiogenesis</subject><subject>Animal models</subject><subject>Animals</subject><subject>Arachidonic acid</subject><subject>Collagen</subject><subject>Cytochrome</subject><subject>Cytochrome P-450 CYP2J2</subject><subject>Cytochrome P-450 Enzyme System - drug effects</subject><subject>Cytochrome P-450 Enzyme System - genetics</subject><subject>Cytochrome P-450 Enzyme System - metabolism</subject><subject>Cytochrome P450</subject><subject>Cytokines</subject><subject>Cytokines - analysis</subject><subject>Cytokines - metabolism</subject><subject>Diabetes</subject><subject>Diabetes Complications - metabolism</subject><subject>Diabetes mellitus</subject><subject>Epoxidation</subject><subject>Gelatinase B</subject><subject>Gene expression</subject><subject>Granulation</subject><subject>Infiltration</subject><subject>Inflammation</subject><subject>Laboratory Medicine</subject><subject>Macrophages</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Obese</subject><subject>mRNA</subject><subject>Pathology</subject><subject>Protein expression</subject><subject>research-article</subject><subject>Rodents</subject><subject>Skin</subject><subject>Skin Ulcer - metabolism</subject><subject>Tissues</subject><subject>Wound healing</subject><subject>Wound Healing - drug effects</subject><issn>0023-6837</issn><issn>1530-0307</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNpNkTtPw0AQhE8IRELgB9Cgk2igcLiHzz6XyOIlIZECCiprbW-ci-yz8Z2B_HscJSCqLebTzGqGkHPO5pxJfVNDbuwnOj8XjMdzwQ_IlCvJAiZZfEimjAkZRFrGE3Li3JoxHoaROiYToSVPmI6mpE43vi1WfdsgXYSK0av0fXFNsWu_NxVacOgoONq1Hq03UFMPfYXeUWOpXyFtwEKFzSjSdklN04HpsaSlgRy9KehXO9iSrhBqY6tTcrSE2uHZ_s7I2_3da_oYPL88PKW3z0HH48QHJagkCiGJE4wEywvGBVcQasFlznWCWiut4zwplAxlIeUSeBzlErSWAhVfyhm53Pl2ffsxjP1k63bo7RiZ8YSHWoYiEiN1saeGvMEy63rTQL_JfssZAbED3CjZCvt_NizbLpD9LZBtF8jGD38AzzZ4QA</recordid><startdate>20170701</startdate><enddate>20170701</enddate><creator>Zhao, Huichen</creator><creator>Chen, Jicui</creator><creator>Chai, Jiachao</creator><creator>Zhang, Yuchao</creator><creator>Yu, Cong</creator><creator>Pan, Zhe</creator><creator>Gao, Peng</creator><creator>Zong, Chen</creator><creator>Guan, Qingbo</creator><creator>Fu, Yuqin</creator><creator>Liu, Yuantao</creator><general>Nature Publishing Group US</general><general>Nature Publishing Group</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>3V.</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7T5</scope><scope>7T7</scope><scope>7TK</scope><scope>7TM</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope></search><sort><creationdate>20170701</creationdate><title>Cytochrome P450 (CYP) epoxygenases as potential targets in the management of impaired diabetic wound healing</title><author>Zhao, Huichen ; Chen, Jicui ; Chai, Jiachao ; Zhang, Yuchao ; Yu, Cong ; Pan, Zhe ; Gao, Peng ; Zong, Chen ; Guan, Qingbo ; Fu, Yuqin ; Liu, Yuantao</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p179t-da5964a979e620bc01215a48213b189e885887b9c5343c33fa176b3a8832e51f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>631/337/2265</topic><topic>64/60</topic><topic>692/163/2743/137/138</topic><topic>8,11,14-Eicosatrienoic Acid - 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metabolism</topic><topic>Tissues</topic><topic>Wound healing</topic><topic>Wound Healing - drug effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhao, Huichen</creatorcontrib><creatorcontrib>Chen, Jicui</creatorcontrib><creatorcontrib>Chai, Jiachao</creatorcontrib><creatorcontrib>Zhang, Yuchao</creatorcontrib><creatorcontrib>Yu, Cong</creatorcontrib><creatorcontrib>Pan, Zhe</creatorcontrib><creatorcontrib>Gao, Peng</creatorcontrib><creatorcontrib>Zong, Chen</creatorcontrib><creatorcontrib>Guan, Qingbo</creatorcontrib><creatorcontrib>Fu, Yuqin</creatorcontrib><creatorcontrib>Liu, Yuantao</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>ProQuest Central (Corporate)</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Immunology Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</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>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science 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 Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</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><jtitle>Laboratory investigation</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhao, Huichen</au><au>Chen, Jicui</au><au>Chai, Jiachao</au><au>Zhang, Yuchao</au><au>Yu, Cong</au><au>Pan, Zhe</au><au>Gao, Peng</au><au>Zong, Chen</au><au>Guan, Qingbo</au><au>Fu, Yuqin</au><au>Liu, Yuantao</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cytochrome P450 (CYP) epoxygenases as potential targets in the management of impaired diabetic wound healing</atitle><jtitle>Laboratory investigation</jtitle><stitle>Lab Invest</stitle><addtitle>Lab Invest</addtitle><date>2017-07-01</date><risdate>2017</risdate><volume>97</volume><issue>7</issue><spage>782</spage><epage>791</epage><pages>782-791</pages><issn>0023-6837</issn><eissn>1530-0307</eissn><abstract>Epoxyeicosatrienoic acids (EETs) are the epoxidation products of arachidonic acid catalyzed by cytochrome P450 (CYP) epoxygenases, which possess multiple biological activities. In the present study, we aimed to explore the role and effects of CYP epoxygenases/EETs in wound healing in ob/ob mice. Full-thickness skin dorsal wounds were made on ob/ob mice and C57BL/6 control mice. The mRNA and protein expression of CYP epoxygenases were determined in granulation tissues of wounds. Effects of EETs on wound healing were evaluated. Inflammation and angiogenesis in wounds were also observed. Compared with C57BL/6 mice, the mRNA and protein expression of CYP2C65 and CYP2J6 in the granulation tissues in ob/ob mice were significantly reduced. 11,12-EET treatment significantly improved wound healing in ob/ob mice, whereas 14,15-EEZE, an EET antagonist, showed the opposite effect. 11,12-EET treatment decreased neutrophil and macrophage infiltration to the wound sites, resulting in reduced production of inflammatory cytokines, decreased MMP-9 expression, and increased collagen accumulation in the granulation tissues of ob/ob mice. In addition, 11,12-EET increased angiogenesis in the granulation tissues of wounds in ob/ob mice. These findings indicate that reduced expression of CYP epoxygenases may contribute to impaired diabetic wound healing, and exogenous EETs may improve diabetic wound healing by modulating inflammation and angiogenesis.</abstract><cop>New York</cop><pub>Nature Publishing Group US</pub><pmid>28319086</pmid><doi>10.1038/labinvest.2017.21</doi><tpages>10</tpages></addata></record> |
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| subjects | 631/337/2265 64/60 692/163/2743/137/138 8,11,14-Eicosatrienoic Acid - analogs & derivatives 8,11,14-Eicosatrienoic Acid - pharmacology 82/51 82/80 96/1 Angiogenesis Animal models Animals Arachidonic acid Collagen Cytochrome Cytochrome P-450 CYP2J2 Cytochrome P-450 Enzyme System - drug effects Cytochrome P-450 Enzyme System - genetics Cytochrome P-450 Enzyme System - metabolism Cytochrome P450 Cytokines Cytokines - analysis Cytokines - metabolism Diabetes Diabetes Complications - metabolism Diabetes mellitus Epoxidation Gelatinase B Gene expression Granulation Infiltration Inflammation Laboratory Medicine Macrophages Medicine Medicine & Public Health Mice Mice, Inbred C57BL Mice, Obese mRNA Pathology Protein expression research-article Rodents Skin Skin Ulcer - metabolism Tissues Wound healing Wound Healing - drug effects |
| title | Cytochrome P450 (CYP) epoxygenases as potential targets in the management of impaired diabetic wound healing |
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