Adipose mesenchymal stem cell-derived exosomes accelerate skin wound healing via the lncRNA H19/miR-19b/SOX9 axis
It has been reported that adipose mesenchymal stem cells (ADSCs) accelerate wound healing. Moreover, exosomes, which serve as paracrine factors, play a vital role in wound healing. However, the mechanism remains unclear. This research aimed to determine the roles of exosomes derived from ADSCs (ADSC...
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description | It has been reported that adipose mesenchymal stem cells (ADSCs) accelerate wound healing. Moreover, exosomes, which serve as paracrine factors, play a vital role in wound healing. However, the mechanism remains unclear. This research aimed to determine the roles of exosomes derived from ADSCs (ADSC-Exos) in wound skin tissue repair. Flow cytometry and electron microscopy were carried out to identify ADSCs and ADSC-Exos, respectively; RT-qPCR was performed to assess the lncRNA H19 (H19), microRNA19b (miR-19b) and SRY-related high-mobility-group box 9 (SOX9) levels; Western blotting was carried out to evaluate collagen and β-catenin expression; CCK-8, scratch and transwell assays were conducted to evaluate human skin fibroblast (HSF) cell proliferation, migration and invasion, respectively; the potential binding sites between H19 and miR-19b, miR-19b and SOX9 were detected by dual-luciferase reporter gene assay and RIP assay; and H&E staining was conducted to observe skin wound tissues. ADSC-Exos accelerated the proliferation, migration and invasion of HSF cells via H19. H19 acts as a molecular sponge towards miR-19b, which targets SOX9. ADSC-Exos inhibited miR-19b expression via H19, resulting in accelerated HSF proliferation, migration and invasion. ADSC-Exos upregulated SOX9 to activate the Wnt/β-catenin pathway, resulting in accelerated HSF cell proliferation, migration and invasion, and ADSC-Exos promoted skin wound healing via H19 in mice.
The high expression of H19 in ADSC-Exos may upregulate SOX9 expression via miR-19b to accelerate wound healing of skin tissues. Our study may provide novel perspectives for therapy to accelerate skin wound healing.
This study reveals that the long non-coding RNA H19 is highly expressed in exosomes derived from adipose mesenchymal stem cells and accelerates the proliferation, migration and invasion of human skin fibroblasts by upregulation of SOX9 and activation of the Wnt/β-catenin pathway The authors show that H19 affects SOX9 expression via the microRNA miR-19b to promote wound healing in injured skin. |
doi_str_mv | 10.1038/s41374-021-00611-8 |
format | Article |
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The high expression of H19 in ADSC-Exos may upregulate SOX9 expression via miR-19b to accelerate wound healing of skin tissues. Our study may provide novel perspectives for therapy to accelerate skin wound healing.
This study reveals that the long non-coding RNA H19 is highly expressed in exosomes derived from adipose mesenchymal stem cells and accelerates the proliferation, migration and invasion of human skin fibroblasts by upregulation of SOX9 and activation of the Wnt/β-catenin pathway The authors show that H19 affects SOX9 expression via the microRNA miR-19b to promote wound healing in injured skin.</description><identifier>ISSN: 0023-6837</identifier><identifier>EISSN: 1530-0307</identifier><identifier>DOI: 10.1038/s41374-021-00611-8</identifier><identifier>PMID: 34045678</identifier><language>eng</language><publisher>New York: Elsevier Inc</publisher><subject>42/100 ; 631/80 ; 692/308/2171 ; Adipose Tissue - cytology ; Animals ; Assaying ; Binding sites ; Cell growth ; Cell Line ; Cell migration ; Cell proliferation ; Cells, Cultured ; Cholecystokinin ; Collagen ; Electron microscopy ; Evaluation ; Exosomes ; Exosomes - chemistry ; Exosomes - metabolism ; Fibroblasts ; Flow cytometry ; Humans ; Laboratory Medicine ; Male ; Medicine ; Medicine & Public Health ; Mesenchymal stem cells ; Mesenchymal Stem Cells - cytology ; Mice ; Mice, Inbred BALB C ; MicroRNAs - metabolism ; miRNA ; Non-coding RNA ; Paracrine signalling ; Pathology ; Reporter gene ; Ribonucleic acid ; RNA ; RNA, Long Noncoding - metabolism ; Signal Transduction - physiology ; Skin ; Skin - metabolism ; Sox9 protein ; SOX9 Transcription Factor - metabolism ; Stem cell transplantation ; Stem cells ; Tissues ; Western blotting ; Wnt protein ; Wound healing ; Wound Healing - physiology ; β-Catenin</subject><ispartof>Laboratory investigation, 2021-09, Vol.101 (9), p.1254-1266</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</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.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c472t-474107b42e61d8516972ef3fb50b84f7e1874d22132738fff33abb43a508b6303</citedby><cites>FETCH-LOGICAL-c472t-474107b42e61d8516972ef3fb50b84f7e1874d22132738fff33abb43a508b6303</cites><orcidid>0000-0003-0920-4889</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34045678$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Qian, Li</creatorcontrib><creatorcontrib>Pi, Li</creatorcontrib><creatorcontrib>Fang, Bai-Rong</creatorcontrib><creatorcontrib>Meng, Xian-Xi</creatorcontrib><title>Adipose mesenchymal stem cell-derived exosomes accelerate skin wound healing via the lncRNA H19/miR-19b/SOX9 axis</title><title>Laboratory investigation</title><addtitle>Lab Invest</addtitle><addtitle>Lab Invest</addtitle><description>It has been reported that adipose mesenchymal stem cells (ADSCs) accelerate wound healing. Moreover, exosomes, which serve as paracrine factors, play a vital role in wound healing. However, the mechanism remains unclear. This research aimed to determine the roles of exosomes derived from ADSCs (ADSC-Exos) in wound skin tissue repair. Flow cytometry and electron microscopy were carried out to identify ADSCs and ADSC-Exos, respectively; RT-qPCR was performed to assess the lncRNA H19 (H19), microRNA19b (miR-19b) and SRY-related high-mobility-group box 9 (SOX9) levels; Western blotting was carried out to evaluate collagen and β-catenin expression; CCK-8, scratch and transwell assays were conducted to evaluate human skin fibroblast (HSF) cell proliferation, migration and invasion, respectively; the potential binding sites between H19 and miR-19b, miR-19b and SOX9 were detected by dual-luciferase reporter gene assay and RIP assay; and H&E staining was conducted to observe skin wound tissues. ADSC-Exos accelerated the proliferation, migration and invasion of HSF cells via H19. H19 acts as a molecular sponge towards miR-19b, which targets SOX9. ADSC-Exos inhibited miR-19b expression via H19, resulting in accelerated HSF proliferation, migration and invasion. ADSC-Exos upregulated SOX9 to activate the Wnt/β-catenin pathway, resulting in accelerated HSF cell proliferation, migration and invasion, and ADSC-Exos promoted skin wound healing via H19 in mice.
The high expression of H19 in ADSC-Exos may upregulate SOX9 expression via miR-19b to accelerate wound healing of skin tissues. Our study may provide novel perspectives for therapy to accelerate skin wound healing.
This study reveals that the long non-coding RNA H19 is highly expressed in exosomes derived from adipose mesenchymal stem cells and accelerates the proliferation, migration and invasion of human skin fibroblasts by upregulation of SOX9 and activation of the Wnt/β-catenin pathway The authors show that H19 affects SOX9 expression via the microRNA miR-19b to promote wound healing in injured skin.</description><subject>42/100</subject><subject>631/80</subject><subject>692/308/2171</subject><subject>Adipose Tissue - cytology</subject><subject>Animals</subject><subject>Assaying</subject><subject>Binding sites</subject><subject>Cell growth</subject><subject>Cell Line</subject><subject>Cell migration</subject><subject>Cell proliferation</subject><subject>Cells, Cultured</subject><subject>Cholecystokinin</subject><subject>Collagen</subject><subject>Electron microscopy</subject><subject>Evaluation</subject><subject>Exosomes</subject><subject>Exosomes - chemistry</subject><subject>Exosomes - metabolism</subject><subject>Fibroblasts</subject><subject>Flow cytometry</subject><subject>Humans</subject><subject>Laboratory Medicine</subject><subject>Male</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Mesenchymal stem cells</subject><subject>Mesenchymal Stem Cells - 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cytology</topic><topic>Animals</topic><topic>Assaying</topic><topic>Binding sites</topic><topic>Cell growth</topic><topic>Cell Line</topic><topic>Cell migration</topic><topic>Cell proliferation</topic><topic>Cells, Cultured</topic><topic>Cholecystokinin</topic><topic>Collagen</topic><topic>Electron microscopy</topic><topic>Evaluation</topic><topic>Exosomes</topic><topic>Exosomes - chemistry</topic><topic>Exosomes - metabolism</topic><topic>Fibroblasts</topic><topic>Flow cytometry</topic><topic>Humans</topic><topic>Laboratory Medicine</topic><topic>Male</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Mesenchymal stem cells</topic><topic>Mesenchymal Stem Cells - cytology</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>MicroRNAs - metabolism</topic><topic>miRNA</topic><topic>Non-coding RNA</topic><topic>Paracrine signalling</topic><topic>Pathology</topic><topic>Reporter gene</topic><topic>Ribonucleic acid</topic><topic>RNA</topic><topic>RNA, Long Noncoding - metabolism</topic><topic>Signal Transduction - physiology</topic><topic>Skin</topic><topic>Skin - metabolism</topic><topic>Sox9 protein</topic><topic>SOX9 Transcription Factor - metabolism</topic><topic>Stem cell transplantation</topic><topic>Stem cells</topic><topic>Tissues</topic><topic>Western blotting</topic><topic>Wnt protein</topic><topic>Wound healing</topic><topic>Wound Healing - physiology</topic><topic>β-Catenin</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Qian, Li</creatorcontrib><creatorcontrib>Pi, Li</creatorcontrib><creatorcontrib>Fang, Bai-Rong</creatorcontrib><creatorcontrib>Meng, Xian-Xi</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><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>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><collection>MEDLINE - Academic</collection><jtitle>Laboratory investigation</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Qian, Li</au><au>Pi, Li</au><au>Fang, Bai-Rong</au><au>Meng, Xian-Xi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Adipose mesenchymal stem cell-derived exosomes accelerate skin wound healing via the lncRNA H19/miR-19b/SOX9 axis</atitle><jtitle>Laboratory investigation</jtitle><stitle>Lab Invest</stitle><addtitle>Lab Invest</addtitle><date>2021-09-01</date><risdate>2021</risdate><volume>101</volume><issue>9</issue><spage>1254</spage><epage>1266</epage><pages>1254-1266</pages><issn>0023-6837</issn><eissn>1530-0307</eissn><abstract>It has been reported that adipose mesenchymal stem cells (ADSCs) accelerate wound healing. Moreover, exosomes, which serve as paracrine factors, play a vital role in wound healing. However, the mechanism remains unclear. This research aimed to determine the roles of exosomes derived from ADSCs (ADSC-Exos) in wound skin tissue repair. Flow cytometry and electron microscopy were carried out to identify ADSCs and ADSC-Exos, respectively; RT-qPCR was performed to assess the lncRNA H19 (H19), microRNA19b (miR-19b) and SRY-related high-mobility-group box 9 (SOX9) levels; Western blotting was carried out to evaluate collagen and β-catenin expression; CCK-8, scratch and transwell assays were conducted to evaluate human skin fibroblast (HSF) cell proliferation, migration and invasion, respectively; the potential binding sites between H19 and miR-19b, miR-19b and SOX9 were detected by dual-luciferase reporter gene assay and RIP assay; and H&E staining was conducted to observe skin wound tissues. ADSC-Exos accelerated the proliferation, migration and invasion of HSF cells via H19. H19 acts as a molecular sponge towards miR-19b, which targets SOX9. ADSC-Exos inhibited miR-19b expression via H19, resulting in accelerated HSF proliferation, migration and invasion. ADSC-Exos upregulated SOX9 to activate the Wnt/β-catenin pathway, resulting in accelerated HSF cell proliferation, migration and invasion, and ADSC-Exos promoted skin wound healing via H19 in mice.
The high expression of H19 in ADSC-Exos may upregulate SOX9 expression via miR-19b to accelerate wound healing of skin tissues. Our study may provide novel perspectives for therapy to accelerate skin wound healing.
This study reveals that the long non-coding RNA H19 is highly expressed in exosomes derived from adipose mesenchymal stem cells and accelerates the proliferation, migration and invasion of human skin fibroblasts by upregulation of SOX9 and activation of the Wnt/β-catenin pathway The authors show that H19 affects SOX9 expression via the microRNA miR-19b to promote wound healing in injured skin.</abstract><cop>New York</cop><pub>Elsevier Inc</pub><pmid>34045678</pmid><doi>10.1038/s41374-021-00611-8</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0003-0920-4889</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | 42/100 631/80 692/308/2171 Adipose Tissue - cytology Animals Assaying Binding sites Cell growth Cell Line Cell migration Cell proliferation Cells, Cultured Cholecystokinin Collagen Electron microscopy Evaluation Exosomes Exosomes - chemistry Exosomes - metabolism Fibroblasts Flow cytometry Humans Laboratory Medicine Male Medicine Medicine & Public Health Mesenchymal stem cells Mesenchymal Stem Cells - cytology Mice Mice, Inbred BALB C MicroRNAs - metabolism miRNA Non-coding RNA Paracrine signalling Pathology Reporter gene Ribonucleic acid RNA RNA, Long Noncoding - metabolism Signal Transduction - physiology Skin Skin - metabolism Sox9 protein SOX9 Transcription Factor - metabolism Stem cell transplantation Stem cells Tissues Western blotting Wnt protein Wound healing Wound Healing - physiology β-Catenin |
title | Adipose mesenchymal stem cell-derived exosomes accelerate skin wound healing via the lncRNA H19/miR-19b/SOX9 axis |
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