LncRNA GAS5 activates the HIF1A/VEGF pathway by binding to TAF15 to promote wound healing in diabetic foot ulcers
A diabetic foot ulcer (DFU) is one of the most devastating complications of diabetes. It has been reported that lncRNA GAS5 plays a vital role in wound healing in DFUs. However, the specific mechanism remains unclear. In this research, we aimed to investigate the role of GAS5 in wound healing in DFU...
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| description | A diabetic foot ulcer (DFU) is one of the most devastating complications of diabetes. It has been reported that lncRNA GAS5 plays a vital role in wound healing in DFUs. However, the specific mechanism remains unclear. In this research, we aimed to investigate the role of GAS5 in wound healing in DFUs as well as the underlying mechanism. qPCR or western blotting was performed to measure the expression levels of GAS5, HIF1A, VEGF and TAF15. CCK-8 or EdU assays, flow cytometry, wound healing assays and tube formation assays were carried out to assess the proliferation, apoptosis, wound healing and in vitro angiogenesis of HUVECs, respectively. RNA pull-down and RIP assays were performed to verify the interaction between GAS5 and TAF15. ChIP and luciferase assays were conducted to verify the binding of TAF15 to the HIF1A promoter. In the DFU mouse model, H&E and Masson staining were used to determine epidermal and dermal thickness and collagen formation. GAS5 and HIF1A were downregulated in the skin tissues of DFU patients, and GAS5 overexpression promoted cell proliferation, wound healing and tubule formation in HG-treated HUVECs. In addition, GAS5 facilitated HIF1A expression by interacting with TAF15. Rescue assays demonstrated that the suppression of HIF1A/VEGF pathway activation partially reversed the functional roles of GAS5 in HUVECs. Furthermore, GAS5 accelerated wound healing by activating the HIF1A/VEGF pathway in mice with DFUs. GAS5 activates the HIF1A/VEGF pathway by binding to TAF15, resulting in accelerated wound healing in DFUs. Our findings may provide a theoretical basis for the clinical treatment of DFUs.
Long noncoding RNAs GAS5 activates the HIF1A/VEGF pathway by binding to TAF15 (a component of RNA polymerase II), resulting in accelerated wound healing in diabetic foot ulcers. These findings may provide a theoretical basis for clinical treatment. |
| doi_str_mv | 10.1038/s41374-021-00598-2 |
| format | Article |
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Long noncoding RNAs GAS5 activates the HIF1A/VEGF pathway by binding to TAF15 (a component of RNA polymerase II), resulting in accelerated wound healing in diabetic foot ulcers. These findings may provide a theoretical basis for clinical treatment.</description><identifier>ISSN: 0023-6837</identifier><identifier>EISSN: 1530-0307</identifier><identifier>DOI: 10.1038/s41374-021-00598-2</identifier><identifier>PMID: 33875793</identifier><language>eng</language><publisher>New York: Elsevier Inc</publisher><subject>13/31 ; 631/80/304 ; 692/699 ; Adult ; Aged ; Angiogenesis ; Animals ; Apoptosis ; Assaying ; Binding ; Cell proliferation ; Cell Proliferation - genetics ; Cells, Cultured ; Cholecystokinin ; Collagen ; Complications ; Diabetes ; Diabetes mellitus ; Diabetic Foot - metabolism ; Disease Models, Animal ; DNA-directed RNA polymerase ; Feet ; Female ; Flow cytometry ; Foot diseases ; Human Umbilical Vein Endothelial Cells ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit - genetics ; Hypoxia-Inducible Factor 1, alpha Subunit - metabolism ; Laboratory Medicine ; Leg ulcers ; Life Sciences & Biomedicine ; Male ; Medicine ; Medicine & Public Health ; Medicine, Research & Experimental ; Mice ; Middle Aged ; Pathology ; Research & Experimental Medicine ; RNA polymerase ; RNA polymerase II ; RNA, Long Noncoding - genetics ; RNA, Long Noncoding - metabolism ; Science & Technology ; Signal Transduction - genetics ; TATA-Binding Protein Associated Factors - genetics ; TATA-Binding Protein Associated Factors - metabolism ; Ulcers ; Vascular endothelial growth factor ; Vascular Endothelial Growth Factor A - genetics ; Vascular Endothelial Growth Factor A - metabolism ; Western blotting ; Wound healing ; Wound Healing - genetics</subject><ispartof>Laboratory investigation, 2021-08, Vol.101 (8), p.1071-1083</ispartof><rights>2021 United States & Canadian Academy of Pathology</rights><rights>The Author(s), under exclusive licence to United States and Canadian Academy of Pathology 2021. corrected publication 2021</rights><rights>2021. The Author(s), under exclusive licence to United States and Canadian Academy of Pathology.</rights><rights>The Author(s), under exclusive licence to United States and Canadian Academy of Pathology 2021. corrected publication 2021.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>true</woscitedreferencessubscribed><woscitedreferencescount>31</woscitedreferencescount><woscitedreferencesoriginalsourcerecordid>wos000641238100004</woscitedreferencesoriginalsourcerecordid><citedby>FETCH-LOGICAL-c472t-db3b06ac4835af5ad7fddc103b6d644344e5ebc8fb834c939532eb18905678573</citedby><cites>FETCH-LOGICAL-c472t-db3b06ac4835af5ad7fddc103b6d644344e5ebc8fb834c939532eb18905678573</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,781,785,27929,27930,39263</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33875793$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Peng, Wei-Xia</creatorcontrib><creatorcontrib>He, Pei-Xiang</creatorcontrib><creatorcontrib>Liu, Li-Jun</creatorcontrib><creatorcontrib>Zhu, Ting</creatorcontrib><creatorcontrib>Zhong, Ya-Qin</creatorcontrib><creatorcontrib>Xiang, Lin</creatorcontrib><creatorcontrib>Peng, Ke</creatorcontrib><creatorcontrib>Yang, Jing-Jin</creatorcontrib><creatorcontrib>Xiang, Guang-Da</creatorcontrib><title>LncRNA GAS5 activates the HIF1A/VEGF pathway by binding to TAF15 to promote wound healing in diabetic foot ulcers</title><title>Laboratory investigation</title><addtitle>Lab Invest</addtitle><addtitle>LAB INVEST</addtitle><addtitle>Lab Invest</addtitle><description>A diabetic foot ulcer (DFU) is one of the most devastating complications of diabetes. It has been reported that lncRNA GAS5 plays a vital role in wound healing in DFUs. However, the specific mechanism remains unclear. In this research, we aimed to investigate the role of GAS5 in wound healing in DFUs as well as the underlying mechanism. qPCR or western blotting was performed to measure the expression levels of GAS5, HIF1A, VEGF and TAF15. CCK-8 or EdU assays, flow cytometry, wound healing assays and tube formation assays were carried out to assess the proliferation, apoptosis, wound healing and in vitro angiogenesis of HUVECs, respectively. RNA pull-down and RIP assays were performed to verify the interaction between GAS5 and TAF15. ChIP and luciferase assays were conducted to verify the binding of TAF15 to the HIF1A promoter. In the DFU mouse model, H&E and Masson staining were used to determine epidermal and dermal thickness and collagen formation. GAS5 and HIF1A were downregulated in the skin tissues of DFU patients, and GAS5 overexpression promoted cell proliferation, wound healing and tubule formation in HG-treated HUVECs. In addition, GAS5 facilitated HIF1A expression by interacting with TAF15. Rescue assays demonstrated that the suppression of HIF1A/VEGF pathway activation partially reversed the functional roles of GAS5 in HUVECs. Furthermore, GAS5 accelerated wound healing by activating the HIF1A/VEGF pathway in mice with DFUs. GAS5 activates the HIF1A/VEGF pathway by binding to TAF15, resulting in accelerated wound healing in DFUs. Our findings may provide a theoretical basis for the clinical treatment of DFUs.
Long noncoding RNAs GAS5 activates the HIF1A/VEGF pathway by binding to TAF15 (a component of RNA polymerase II), resulting in accelerated wound healing in diabetic foot ulcers. These findings may provide a theoretical basis for clinical treatment.</description><subject>13/31</subject><subject>631/80/304</subject><subject>692/699</subject><subject>Adult</subject><subject>Aged</subject><subject>Angiogenesis</subject><subject>Animals</subject><subject>Apoptosis</subject><subject>Assaying</subject><subject>Binding</subject><subject>Cell proliferation</subject><subject>Cell Proliferation - genetics</subject><subject>Cells, Cultured</subject><subject>Cholecystokinin</subject><subject>Collagen</subject><subject>Complications</subject><subject>Diabetes</subject><subject>Diabetes mellitus</subject><subject>Diabetic Foot - metabolism</subject><subject>Disease Models, Animal</subject><subject>DNA-directed RNA polymerase</subject><subject>Feet</subject><subject>Female</subject><subject>Flow cytometry</subject><subject>Foot diseases</subject><subject>Human Umbilical Vein Endothelial Cells</subject><subject>Humans</subject><subject>Hypoxia-Inducible Factor 1, alpha Subunit - genetics</subject><subject>Hypoxia-Inducible Factor 1, alpha Subunit - metabolism</subject><subject>Laboratory Medicine</subject><subject>Leg ulcers</subject><subject>Life Sciences & Biomedicine</subject><subject>Male</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Medicine, Research & Experimental</subject><subject>Mice</subject><subject>Middle Aged</subject><subject>Pathology</subject><subject>Research & Experimental Medicine</subject><subject>RNA polymerase</subject><subject>RNA polymerase II</subject><subject>RNA, Long Noncoding - genetics</subject><subject>RNA, Long Noncoding - metabolism</subject><subject>Science & Technology</subject><subject>Signal Transduction - genetics</subject><subject>TATA-Binding Protein Associated Factors - genetics</subject><subject>TATA-Binding Protein Associated Factors - metabolism</subject><subject>Ulcers</subject><subject>Vascular endothelial growth factor</subject><subject>Vascular Endothelial Growth Factor A - 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genetics</topic><topic>Cells, Cultured</topic><topic>Cholecystokinin</topic><topic>Collagen</topic><topic>Complications</topic><topic>Diabetes</topic><topic>Diabetes mellitus</topic><topic>Diabetic Foot - metabolism</topic><topic>Disease Models, Animal</topic><topic>DNA-directed RNA polymerase</topic><topic>Feet</topic><topic>Female</topic><topic>Flow cytometry</topic><topic>Foot diseases</topic><topic>Human Umbilical Vein Endothelial Cells</topic><topic>Humans</topic><topic>Hypoxia-Inducible Factor 1, alpha Subunit - genetics</topic><topic>Hypoxia-Inducible Factor 1, alpha Subunit - metabolism</topic><topic>Laboratory Medicine</topic><topic>Leg ulcers</topic><topic>Life Sciences & Biomedicine</topic><topic>Male</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Medicine, Research & Experimental</topic><topic>Mice</topic><topic>Middle Aged</topic><topic>Pathology</topic><topic>Research & Experimental Medicine</topic><topic>RNA polymerase</topic><topic>RNA polymerase II</topic><topic>RNA, Long Noncoding - 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Academic</collection><jtitle>Laboratory investigation</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Peng, Wei-Xia</au><au>He, Pei-Xiang</au><au>Liu, Li-Jun</au><au>Zhu, Ting</au><au>Zhong, Ya-Qin</au><au>Xiang, Lin</au><au>Peng, Ke</au><au>Yang, Jing-Jin</au><au>Xiang, Guang-Da</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>LncRNA GAS5 activates the HIF1A/VEGF pathway by binding to TAF15 to promote wound healing in diabetic foot ulcers</atitle><jtitle>Laboratory investigation</jtitle><stitle>Lab Invest</stitle><stitle>LAB INVEST</stitle><addtitle>Lab Invest</addtitle><date>2021-08-01</date><risdate>2021</risdate><volume>101</volume><issue>8</issue><spage>1071</spage><epage>1083</epage><pages>1071-1083</pages><issn>0023-6837</issn><eissn>1530-0307</eissn><abstract>A diabetic foot ulcer (DFU) is one of the most devastating complications of diabetes. It has been reported that lncRNA GAS5 plays a vital role in wound healing in DFUs. However, the specific mechanism remains unclear. In this research, we aimed to investigate the role of GAS5 in wound healing in DFUs as well as the underlying mechanism. qPCR or western blotting was performed to measure the expression levels of GAS5, HIF1A, VEGF and TAF15. CCK-8 or EdU assays, flow cytometry, wound healing assays and tube formation assays were carried out to assess the proliferation, apoptosis, wound healing and in vitro angiogenesis of HUVECs, respectively. RNA pull-down and RIP assays were performed to verify the interaction between GAS5 and TAF15. ChIP and luciferase assays were conducted to verify the binding of TAF15 to the HIF1A promoter. In the DFU mouse model, H&E and Masson staining were used to determine epidermal and dermal thickness and collagen formation. GAS5 and HIF1A were downregulated in the skin tissues of DFU patients, and GAS5 overexpression promoted cell proliferation, wound healing and tubule formation in HG-treated HUVECs. In addition, GAS5 facilitated HIF1A expression by interacting with TAF15. Rescue assays demonstrated that the suppression of HIF1A/VEGF pathway activation partially reversed the functional roles of GAS5 in HUVECs. Furthermore, GAS5 accelerated wound healing by activating the HIF1A/VEGF pathway in mice with DFUs. GAS5 activates the HIF1A/VEGF pathway by binding to TAF15, resulting in accelerated wound healing in DFUs. Our findings may provide a theoretical basis for the clinical treatment of DFUs.
Long noncoding RNAs GAS5 activates the HIF1A/VEGF pathway by binding to TAF15 (a component of RNA polymerase II), resulting in accelerated wound healing in diabetic foot ulcers. These findings may provide a theoretical basis for clinical treatment.</abstract><cop>New York</cop><pub>Elsevier Inc</pub><pmid>33875793</pmid><doi>10.1038/s41374-021-00598-2</doi><tpages>13</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Laboratory investigation, 2021-08, Vol.101 (8), p.1071-1083 |
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| language | eng |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Web of Science - Science Citation Index Expanded - 2021<img src="https://exlibris-pub.s3.amazonaws.com/fromwos-v2.jpg" />; Alma/SFX Local Collection |
| subjects | 13/31 631/80/304 692/699 Adult Aged Angiogenesis Animals Apoptosis Assaying Binding Cell proliferation Cell Proliferation - genetics Cells, Cultured Cholecystokinin Collagen Complications Diabetes Diabetes mellitus Diabetic Foot - metabolism Disease Models, Animal DNA-directed RNA polymerase Feet Female Flow cytometry Foot diseases Human Umbilical Vein Endothelial Cells Humans Hypoxia-Inducible Factor 1, alpha Subunit - genetics Hypoxia-Inducible Factor 1, alpha Subunit - metabolism Laboratory Medicine Leg ulcers Life Sciences & Biomedicine Male Medicine Medicine & Public Health Medicine, Research & Experimental Mice Middle Aged Pathology Research & Experimental Medicine RNA polymerase RNA polymerase II RNA, Long Noncoding - genetics RNA, Long Noncoding - metabolism Science & Technology Signal Transduction - genetics TATA-Binding Protein Associated Factors - genetics TATA-Binding Protein Associated Factors - metabolism Ulcers Vascular endothelial growth factor Vascular Endothelial Growth Factor A - genetics Vascular Endothelial Growth Factor A - metabolism Western blotting Wound healing Wound Healing - genetics |
| title | LncRNA GAS5 activates the HIF1A/VEGF pathway by binding to TAF15 to promote wound healing in diabetic foot ulcers |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-15T08%3A01%3A27IST&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=LncRNA%20GAS5%20activates%20the%20HIF1A/VEGF%20pathway%20by%20binding%20to%20TAF15%20to%20promote%20wound%20healing%20in%20diabetic%20foot%20ulcers&rft.jtitle=Laboratory%20investigation&rft.au=Peng,%20Wei-Xia&rft.date=2021-08-01&rft.volume=101&rft.issue=8&rft.spage=1071&rft.epage=1083&rft.pages=1071-1083&rft.issn=0023-6837&rft.eissn=1530-0307&rft_id=info:doi/10.1038/s41374-021-00598-2&rft_dat=%3Cproquest_pubme%3E2515689449%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=2553398557&rft_id=info:pmid/33875793&rft_els_id=S0023683722005992&rfr_iscdi=true |