GDF11 promotes wound healing in diabetic mice via stimulating HIF-1ɑ-VEGF/SDF-1ɑ-mediated endothelial progenitor cell mobilization and neovascularization
Non-healing diabetic wounds (DW) are a serious clinical problem that remained poorly understood. We recently found that topical application of growth differentiation factor 11 (GDF11) accelerated skin wound healing in both Type 1 DM (T1DM) and genetically engineered Type 2 diabetic db/db (T2DM) mice...
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| Veröffentlicht in: | Acta pharmacologica Sinica 2023-05, Vol.44 (5), p.999-1013 |
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| creator | Zhang, Ying Zhang, Yi-yuan Pan, Zhen-wei Li, Qing-qi Sun, Li-hua Li, Xin Gong, Man-yu Yang, Xue-wen Wang, Yan-ying Li, Hao-dong Xuan, Li-na Shao, Ying-chun Li, Meng-meng Zhang, Ming-yu Yu, Qi Li, Zhange Zhang, Xiao-fang Liu, Dong-hua Zhu, Yan-meng Tan, Zhong-yue Zhang, Yuan-yuan Liu, Yun-qi Zhang, Yong Jiao, Lei Yang, Bao-feng |
| description | Non-healing diabetic wounds (DW) are a serious clinical problem that remained poorly understood. We recently found that topical application of growth differentiation factor 11 (GDF11) accelerated skin wound healing in both Type 1 DM (T1DM) and genetically engineered Type 2 diabetic
db/db
(T2DM) mice. In the present study, we elucidated the cellular and molecular mechanisms underlying the action of GDF11 on healing of small skin wound. Single round-shape full-thickness wound of 5-mm diameter with muscle and bone exposed was made on mouse dorsum using a sterile punch biopsy 7 days following the onset of DM. Recombinant human GDF11 (rGDF11, 50 ng/mL, 10 μL) was topically applied onto the wound area twice a day until epidermal closure (maximum 14 days). Digital images of wound were obtained once a day from D0 to D14 post-wounding. We showed that topical application of GDF11 accelerated the healing of full-thickness skin wounds in both type 1 and type 2 diabetic mice, even after GDF8 (a muscle growth factor) had been silenced. At the cellular level, GDF11 significantly facilitated neovascularization to enhance regeneration of skin tissues by stimulating mobilization, migration and homing of endothelial progenitor cells (EPCs) to the wounded area. At the molecular level, GDF11 greatly increased HIF-1ɑ expression to enhance the activities of VEGF and SDF-1ɑ, thereby neovascularization. We found that endogenous GDF11 level was robustly decreased in skin tissue of diabetic wounds. The specific antibody against GDF11 or silence of GDF11 by siRNA in healthy mice mimicked the non-healing property of diabetic wound. Thus, we demonstrate that GDF11 promotes diabetic wound healing via stimulating endothelial progenitor cells mobilization and neovascularization mediated by HIF-1ɑ-VEGF/SDF-1ɑ pathway. Our results support the potential of GDF11 as a therapeutic agent for non-healing DW. |
| doi_str_mv | 10.1038/s41401-022-01013-2 |
| format | Article |
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db/db
(T2DM) mice. In the present study, we elucidated the cellular and molecular mechanisms underlying the action of GDF11 on healing of small skin wound. Single round-shape full-thickness wound of 5-mm diameter with muscle and bone exposed was made on mouse dorsum using a sterile punch biopsy 7 days following the onset of DM. Recombinant human GDF11 (rGDF11, 50 ng/mL, 10 μL) was topically applied onto the wound area twice a day until epidermal closure (maximum 14 days). Digital images of wound were obtained once a day from D0 to D14 post-wounding. We showed that topical application of GDF11 accelerated the healing of full-thickness skin wounds in both type 1 and type 2 diabetic mice, even after GDF8 (a muscle growth factor) had been silenced. At the cellular level, GDF11 significantly facilitated neovascularization to enhance regeneration of skin tissues by stimulating mobilization, migration and homing of endothelial progenitor cells (EPCs) to the wounded area. At the molecular level, GDF11 greatly increased HIF-1ɑ expression to enhance the activities of VEGF and SDF-1ɑ, thereby neovascularization. We found that endogenous GDF11 level was robustly decreased in skin tissue of diabetic wounds. The specific antibody against GDF11 or silence of GDF11 by siRNA in healthy mice mimicked the non-healing property of diabetic wound. Thus, we demonstrate that GDF11 promotes diabetic wound healing via stimulating endothelial progenitor cells mobilization and neovascularization mediated by HIF-1ɑ-VEGF/SDF-1ɑ pathway. Our results support the potential of GDF11 as a therapeutic agent for non-healing DW.</description><identifier>ISSN: 1671-4083</identifier><identifier>EISSN: 1745-7254</identifier><identifier>DOI: 10.1038/s41401-022-01013-2</identifier><identifier>PMID: 36347996</identifier><language>eng</language><publisher>Singapore: Springer Nature Singapore</publisher><subject>Animals ; Biomedical and Life Sciences ; Biomedicine ; Biopsy ; Bone Morphogenetic Proteins - metabolism ; Chemokine CXCL12 - drug effects ; Chemokine CXCL12 - metabolism ; Diabetes ; Diabetes mellitus ; Diabetes Mellitus, Experimental - complications ; Diabetes Mellitus, Experimental - drug therapy ; Diabetes Mellitus, Experimental - metabolism ; Diabetes Mellitus, Type 2 - drug therapy ; Diabetes Mellitus, Type 2 - metabolism ; Endothelial Progenitor Cells - metabolism ; Endothelial Progenitor Cells - pathology ; Genetic engineering ; Growth differentiation factor 11 ; Growth Differentiation Factors - metabolism ; Growth Differentiation Factors - therapeutic use ; Homing behavior ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit - drug effects ; Hypoxia-Inducible Factor 1, alpha Subunit - metabolism ; Immunology ; Internal Medicine ; Medical Microbiology ; Mice ; Molecular modelling ; Neovascularization, Physiologic ; Pharmacology/Toxicology ; Progenitor cells ; Recombinant Proteins - metabolism ; Recombinant Proteins - therapeutic use ; Regeneration ; siRNA ; Skin ; Topical application ; Vaccine ; Vascular endothelial growth factor ; Vascular Endothelial Growth Factor A - drug effects ; Vascular Endothelial Growth Factor A - metabolism ; Vascularization ; Wound healing ; Wound Healing - drug effects</subject><ispartof>Acta pharmacologica Sinica, 2023-05, Vol.44 (5), p.999-1013</ispartof><rights>The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society 2022. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.</rights><rights>2022. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.</rights><rights>The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society 2022, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3902-2259d4a37a41428283ba26a5a11892963b96773c126c8fe78faffaf8998b18793</citedby><cites>FETCH-LOGICAL-c3902-2259d4a37a41428283ba26a5a11892963b96773c126c8fe78faffaf8998b18793</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/PMC10104842/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10104842/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,315,728,781,785,886,27928,27929,53795,53797</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36347996$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhang, Ying</creatorcontrib><creatorcontrib>Zhang, Yi-yuan</creatorcontrib><creatorcontrib>Pan, Zhen-wei</creatorcontrib><creatorcontrib>Li, Qing-qi</creatorcontrib><creatorcontrib>Sun, Li-hua</creatorcontrib><creatorcontrib>Li, Xin</creatorcontrib><creatorcontrib>Gong, Man-yu</creatorcontrib><creatorcontrib>Yang, Xue-wen</creatorcontrib><creatorcontrib>Wang, Yan-ying</creatorcontrib><creatorcontrib>Li, Hao-dong</creatorcontrib><creatorcontrib>Xuan, Li-na</creatorcontrib><creatorcontrib>Shao, Ying-chun</creatorcontrib><creatorcontrib>Li, Meng-meng</creatorcontrib><creatorcontrib>Zhang, Ming-yu</creatorcontrib><creatorcontrib>Yu, Qi</creatorcontrib><creatorcontrib>Li, Zhange</creatorcontrib><creatorcontrib>Zhang, Xiao-fang</creatorcontrib><creatorcontrib>Liu, Dong-hua</creatorcontrib><creatorcontrib>Zhu, Yan-meng</creatorcontrib><creatorcontrib>Tan, Zhong-yue</creatorcontrib><creatorcontrib>Zhang, Yuan-yuan</creatorcontrib><creatorcontrib>Liu, Yun-qi</creatorcontrib><creatorcontrib>Zhang, Yong</creatorcontrib><creatorcontrib>Jiao, Lei</creatorcontrib><creatorcontrib>Yang, Bao-feng</creatorcontrib><title>GDF11 promotes wound healing in diabetic mice via stimulating HIF-1ɑ-VEGF/SDF-1ɑ-mediated endothelial progenitor cell mobilization and neovascularization</title><title>Acta pharmacologica Sinica</title><addtitle>Acta Pharmacol Sin</addtitle><addtitle>Acta Pharmacol Sin</addtitle><description>Non-healing diabetic wounds (DW) are a serious clinical problem that remained poorly understood. We recently found that topical application of growth differentiation factor 11 (GDF11) accelerated skin wound healing in both Type 1 DM (T1DM) and genetically engineered Type 2 diabetic
db/db
(T2DM) mice. In the present study, we elucidated the cellular and molecular mechanisms underlying the action of GDF11 on healing of small skin wound. Single round-shape full-thickness wound of 5-mm diameter with muscle and bone exposed was made on mouse dorsum using a sterile punch biopsy 7 days following the onset of DM. Recombinant human GDF11 (rGDF11, 50 ng/mL, 10 μL) was topically applied onto the wound area twice a day until epidermal closure (maximum 14 days). Digital images of wound were obtained once a day from D0 to D14 post-wounding. We showed that topical application of GDF11 accelerated the healing of full-thickness skin wounds in both type 1 and type 2 diabetic mice, even after GDF8 (a muscle growth factor) had been silenced. At the cellular level, GDF11 significantly facilitated neovascularization to enhance regeneration of skin tissues by stimulating mobilization, migration and homing of endothelial progenitor cells (EPCs) to the wounded area. At the molecular level, GDF11 greatly increased HIF-1ɑ expression to enhance the activities of VEGF and SDF-1ɑ, thereby neovascularization. We found that endogenous GDF11 level was robustly decreased in skin tissue of diabetic wounds. The specific antibody against GDF11 or silence of GDF11 by siRNA in healthy mice mimicked the non-healing property of diabetic wound. Thus, we demonstrate that GDF11 promotes diabetic wound healing via stimulating endothelial progenitor cells mobilization and neovascularization mediated by HIF-1ɑ-VEGF/SDF-1ɑ pathway. Our results support the potential of GDF11 as a therapeutic agent for non-healing DW.</description><subject>Animals</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Biopsy</subject><subject>Bone Morphogenetic Proteins - metabolism</subject><subject>Chemokine CXCL12 - drug effects</subject><subject>Chemokine CXCL12 - metabolism</subject><subject>Diabetes</subject><subject>Diabetes mellitus</subject><subject>Diabetes Mellitus, Experimental - complications</subject><subject>Diabetes Mellitus, Experimental - drug therapy</subject><subject>Diabetes Mellitus, Experimental - metabolism</subject><subject>Diabetes Mellitus, Type 2 - drug therapy</subject><subject>Diabetes Mellitus, Type 2 - metabolism</subject><subject>Endothelial Progenitor Cells - metabolism</subject><subject>Endothelial Progenitor Cells - pathology</subject><subject>Genetic engineering</subject><subject>Growth differentiation factor 11</subject><subject>Growth Differentiation Factors - metabolism</subject><subject>Growth Differentiation Factors - therapeutic use</subject><subject>Homing behavior</subject><subject>Humans</subject><subject>Hypoxia-Inducible Factor 1, alpha Subunit - drug effects</subject><subject>Hypoxia-Inducible Factor 1, alpha Subunit - metabolism</subject><subject>Immunology</subject><subject>Internal Medicine</subject><subject>Medical Microbiology</subject><subject>Mice</subject><subject>Molecular modelling</subject><subject>Neovascularization, Physiologic</subject><subject>Pharmacology/Toxicology</subject><subject>Progenitor cells</subject><subject>Recombinant Proteins - metabolism</subject><subject>Recombinant Proteins - therapeutic use</subject><subject>Regeneration</subject><subject>siRNA</subject><subject>Skin</subject><subject>Topical application</subject><subject>Vaccine</subject><subject>Vascular endothelial growth factor</subject><subject>Vascular Endothelial Growth Factor A - drug effects</subject><subject>Vascular Endothelial Growth Factor A - metabolism</subject><subject>Vascularization</subject><subject>Wound healing</subject><subject>Wound Healing - drug effects</subject><issn>1671-4083</issn><issn>1745-7254</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp9UU2PFCEQJUbjrqN_wIMh8eIFlwKmgZMxuzuzm2ziwY8robuZGTbdMEL3GP0Xnv1F_itpe1w_DiYkUNSrV_XqIfQU6EugXJ1lAYICoYwRChQ4YffQKUixJJItxf3yriQQQRU_QY9yvqWUMw76ITrhFRdS6-oUfVtfrADwPsU-Di7jT3EMLd452_mwxT7g1tvaDb7BvW8cPniL8-D7sbPDBLi6XhH4_pV8uFyvzt5ezEHvStHgWuxCG4ed67ztpg5bF_wQE25c1-E-1r7zXwpNDNiWnsHFg81NYU7H78fowcZ22T053gv0fnX57vyK3LxZX5-_viEN15QRxpa6FZZLW_bBFFO8tqyySwugNNMVr3UlJW-AVY3aOKk2dlOO0lrVoKTmC_Rq5t2PdZm9cWFItjP75HubPptovfk7E_zObOPBlKVToQQrDC-ODCl-HF0eTO_zJNMWVWM2THJRQTWZtEDP_4HexjGFos8wNdmogE8oNqOaFHNObnM3DVAzmW9m800x3_w030xTPPtTx13JL7cLgM-AXFJh69Lv3v-h_QFl6Lw6</recordid><startdate>20230501</startdate><enddate>20230501</enddate><creator>Zhang, Ying</creator><creator>Zhang, Yi-yuan</creator><creator>Pan, Zhen-wei</creator><creator>Li, Qing-qi</creator><creator>Sun, Li-hua</creator><creator>Li, Xin</creator><creator>Gong, Man-yu</creator><creator>Yang, Xue-wen</creator><creator>Wang, Yan-ying</creator><creator>Li, Hao-dong</creator><creator>Xuan, Li-na</creator><creator>Shao, Ying-chun</creator><creator>Li, Meng-meng</creator><creator>Zhang, Ming-yu</creator><creator>Yu, Qi</creator><creator>Li, Zhange</creator><creator>Zhang, Xiao-fang</creator><creator>Liu, Dong-hua</creator><creator>Zhu, Yan-meng</creator><creator>Tan, Zhong-yue</creator><creator>Zhang, Yuan-yuan</creator><creator>Liu, Yun-qi</creator><creator>Zhang, Yong</creator><creator>Jiao, Lei</creator><creator>Yang, Bao-feng</creator><general>Springer Nature Singapore</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>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QP</scope><scope>7QR</scope><scope>7T5</scope><scope>7TK</scope><scope>7TO</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</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>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><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20230501</creationdate><title>GDF11 promotes wound healing in diabetic mice via stimulating HIF-1ɑ-VEGF/SDF-1ɑ-mediated endothelial progenitor cell mobilization and neovascularization</title><author>Zhang, Ying ; Zhang, Yi-yuan ; Pan, Zhen-wei ; Li, Qing-qi ; Sun, Li-hua ; Li, Xin ; Gong, Man-yu ; Yang, Xue-wen ; Wang, Yan-ying ; Li, Hao-dong ; Xuan, Li-na ; Shao, Ying-chun ; Li, Meng-meng ; Zhang, Ming-yu ; Yu, Qi ; Li, Zhange ; Zhang, Xiao-fang ; Liu, Dong-hua ; Zhu, Yan-meng ; Tan, Zhong-yue ; Zhang, Yuan-yuan ; Liu, Yun-qi ; Zhang, Yong ; Jiao, Lei ; Yang, Bao-feng</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3902-2259d4a37a41428283ba26a5a11892963b96773c126c8fe78faffaf8998b18793</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Animals</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Biopsy</topic><topic>Bone Morphogenetic Proteins - metabolism</topic><topic>Chemokine CXCL12 - drug effects</topic><topic>Chemokine CXCL12 - metabolism</topic><topic>Diabetes</topic><topic>Diabetes mellitus</topic><topic>Diabetes Mellitus, Experimental - complications</topic><topic>Diabetes Mellitus, Experimental - drug therapy</topic><topic>Diabetes Mellitus, Experimental - metabolism</topic><topic>Diabetes Mellitus, Type 2 - drug therapy</topic><topic>Diabetes Mellitus, Type 2 - metabolism</topic><topic>Endothelial Progenitor Cells - metabolism</topic><topic>Endothelial Progenitor Cells - pathology</topic><topic>Genetic engineering</topic><topic>Growth differentiation factor 11</topic><topic>Growth Differentiation Factors - metabolism</topic><topic>Growth Differentiation Factors - therapeutic use</topic><topic>Homing behavior</topic><topic>Humans</topic><topic>Hypoxia-Inducible Factor 1, alpha Subunit - drug effects</topic><topic>Hypoxia-Inducible Factor 1, alpha Subunit - metabolism</topic><topic>Immunology</topic><topic>Internal Medicine</topic><topic>Medical Microbiology</topic><topic>Mice</topic><topic>Molecular modelling</topic><topic>Neovascularization, Physiologic</topic><topic>Pharmacology/Toxicology</topic><topic>Progenitor cells</topic><topic>Recombinant Proteins - metabolism</topic><topic>Recombinant Proteins - therapeutic use</topic><topic>Regeneration</topic><topic>siRNA</topic><topic>Skin</topic><topic>Topical application</topic><topic>Vaccine</topic><topic>Vascular endothelial growth factor</topic><topic>Vascular Endothelial Growth Factor A - drug effects</topic><topic>Vascular Endothelial Growth Factor A - metabolism</topic><topic>Vascularization</topic><topic>Wound healing</topic><topic>Wound Healing - drug effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhang, Ying</creatorcontrib><creatorcontrib>Zhang, Yi-yuan</creatorcontrib><creatorcontrib>Pan, Zhen-wei</creatorcontrib><creatorcontrib>Li, Qing-qi</creatorcontrib><creatorcontrib>Sun, Li-hua</creatorcontrib><creatorcontrib>Li, Xin</creatorcontrib><creatorcontrib>Gong, Man-yu</creatorcontrib><creatorcontrib>Yang, Xue-wen</creatorcontrib><creatorcontrib>Wang, Yan-ying</creatorcontrib><creatorcontrib>Li, Hao-dong</creatorcontrib><creatorcontrib>Xuan, Li-na</creatorcontrib><creatorcontrib>Shao, Ying-chun</creatorcontrib><creatorcontrib>Li, Meng-meng</creatorcontrib><creatorcontrib>Zhang, Ming-yu</creatorcontrib><creatorcontrib>Yu, Qi</creatorcontrib><creatorcontrib>Li, Zhange</creatorcontrib><creatorcontrib>Zhang, Xiao-fang</creatorcontrib><creatorcontrib>Liu, Dong-hua</creatorcontrib><creatorcontrib>Zhu, Yan-meng</creatorcontrib><creatorcontrib>Tan, Zhong-yue</creatorcontrib><creatorcontrib>Zhang, Yuan-yuan</creatorcontrib><creatorcontrib>Liu, Yun-qi</creatorcontrib><creatorcontrib>Zhang, Yong</creatorcontrib><creatorcontrib>Jiao, Lei</creatorcontrib><creatorcontrib>Yang, Bao-feng</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>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Oncogenes and Growth Factors 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>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>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><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Acta pharmacologica Sinica</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhang, Ying</au><au>Zhang, Yi-yuan</au><au>Pan, Zhen-wei</au><au>Li, Qing-qi</au><au>Sun, Li-hua</au><au>Li, Xin</au><au>Gong, Man-yu</au><au>Yang, Xue-wen</au><au>Wang, Yan-ying</au><au>Li, Hao-dong</au><au>Xuan, Li-na</au><au>Shao, Ying-chun</au><au>Li, Meng-meng</au><au>Zhang, Ming-yu</au><au>Yu, Qi</au><au>Li, Zhange</au><au>Zhang, Xiao-fang</au><au>Liu, Dong-hua</au><au>Zhu, Yan-meng</au><au>Tan, Zhong-yue</au><au>Zhang, Yuan-yuan</au><au>Liu, Yun-qi</au><au>Zhang, Yong</au><au>Jiao, Lei</au><au>Yang, Bao-feng</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>GDF11 promotes wound healing in diabetic mice via stimulating HIF-1ɑ-VEGF/SDF-1ɑ-mediated endothelial progenitor cell mobilization and neovascularization</atitle><jtitle>Acta pharmacologica Sinica</jtitle><stitle>Acta Pharmacol Sin</stitle><addtitle>Acta Pharmacol Sin</addtitle><date>2023-05-01</date><risdate>2023</risdate><volume>44</volume><issue>5</issue><spage>999</spage><epage>1013</epage><pages>999-1013</pages><issn>1671-4083</issn><eissn>1745-7254</eissn><abstract>Non-healing diabetic wounds (DW) are a serious clinical problem that remained poorly understood. We recently found that topical application of growth differentiation factor 11 (GDF11) accelerated skin wound healing in both Type 1 DM (T1DM) and genetically engineered Type 2 diabetic
db/db
(T2DM) mice. In the present study, we elucidated the cellular and molecular mechanisms underlying the action of GDF11 on healing of small skin wound. Single round-shape full-thickness wound of 5-mm diameter with muscle and bone exposed was made on mouse dorsum using a sterile punch biopsy 7 days following the onset of DM. Recombinant human GDF11 (rGDF11, 50 ng/mL, 10 μL) was topically applied onto the wound area twice a day until epidermal closure (maximum 14 days). Digital images of wound were obtained once a day from D0 to D14 post-wounding. We showed that topical application of GDF11 accelerated the healing of full-thickness skin wounds in both type 1 and type 2 diabetic mice, even after GDF8 (a muscle growth factor) had been silenced. At the cellular level, GDF11 significantly facilitated neovascularization to enhance regeneration of skin tissues by stimulating mobilization, migration and homing of endothelial progenitor cells (EPCs) to the wounded area. At the molecular level, GDF11 greatly increased HIF-1ɑ expression to enhance the activities of VEGF and SDF-1ɑ, thereby neovascularization. We found that endogenous GDF11 level was robustly decreased in skin tissue of diabetic wounds. The specific antibody against GDF11 or silence of GDF11 by siRNA in healthy mice mimicked the non-healing property of diabetic wound. Thus, we demonstrate that GDF11 promotes diabetic wound healing via stimulating endothelial progenitor cells mobilization and neovascularization mediated by HIF-1ɑ-VEGF/SDF-1ɑ pathway. Our results support the potential of GDF11 as a therapeutic agent for non-healing DW.</abstract><cop>Singapore</cop><pub>Springer Nature Singapore</pub><pmid>36347996</pmid><doi>10.1038/s41401-022-01013-2</doi><tpages>15</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1671-4083 |
| ispartof | Acta pharmacologica Sinica, 2023-05, Vol.44 (5), p.999-1013 |
| issn | 1671-4083 1745-7254 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_10104842 |
| source | MEDLINE; PubMed Central; Alma/SFX Local Collection |
| subjects | Animals Biomedical and Life Sciences Biomedicine Biopsy Bone Morphogenetic Proteins - metabolism Chemokine CXCL12 - drug effects Chemokine CXCL12 - metabolism Diabetes Diabetes mellitus Diabetes Mellitus, Experimental - complications Diabetes Mellitus, Experimental - drug therapy Diabetes Mellitus, Experimental - metabolism Diabetes Mellitus, Type 2 - drug therapy Diabetes Mellitus, Type 2 - metabolism Endothelial Progenitor Cells - metabolism Endothelial Progenitor Cells - pathology Genetic engineering Growth differentiation factor 11 Growth Differentiation Factors - metabolism Growth Differentiation Factors - therapeutic use Homing behavior Humans Hypoxia-Inducible Factor 1, alpha Subunit - drug effects Hypoxia-Inducible Factor 1, alpha Subunit - metabolism Immunology Internal Medicine Medical Microbiology Mice Molecular modelling Neovascularization, Physiologic Pharmacology/Toxicology Progenitor cells Recombinant Proteins - metabolism Recombinant Proteins - therapeutic use Regeneration siRNA Skin Topical application Vaccine Vascular endothelial growth factor Vascular Endothelial Growth Factor A - drug effects Vascular Endothelial Growth Factor A - metabolism Vascularization Wound healing Wound Healing - drug effects |
| title | GDF11 promotes wound healing in diabetic mice via stimulating HIF-1ɑ-VEGF/SDF-1ɑ-mediated endothelial progenitor cell mobilization and neovascularization |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-17T08%3A35%3A00IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=GDF11%20promotes%20wound%20healing%20in%20diabetic%20mice%20via%20stimulating%20HIF-1%C9%91-VEGF/SDF-1%C9%91-mediated%20endothelial%20progenitor%20cell%20mobilization%20and%20neovascularization&rft.jtitle=Acta%20pharmacologica%20Sinica&rft.au=Zhang,%20Ying&rft.date=2023-05-01&rft.volume=44&rft.issue=5&rft.spage=999&rft.epage=1013&rft.pages=999-1013&rft.issn=1671-4083&rft.eissn=1745-7254&rft_id=info:doi/10.1038/s41401-022-01013-2&rft_dat=%3Cproquest_pubme%3E2801018131%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2801018131&rft_id=info:pmid/36347996&rfr_iscdi=true |