Periodontitis‐compromised dental pulp stem cells secrete extracellular vesicles carrying miRNA‐378a promote local angiogenesis by targeting Sufu to activate the Hedgehog/Gli1 signalling
Objectives Previously, our investigations demonstrated robust pro‐angiogenic potentials of extracellular vesicles secreted by periodontitis‐compromised dental pulp stem cells (P‐EVs) when compared to those from healthy DPSCs (H‐EVs), but the underlying mechanism remains unknown. Materials and method...
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| Veröffentlicht in: | Cell proliferation 2021-05, Vol.54 (5), p.e13026-n/a |
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| creator | Zhou, Huan Li, Xuan Wu, Rui‐Xin He, Xiao‐Tao An, Ying Xu, Xin‐Yue Sun, Hai‐Hua Wu, Li‐An Chen, Fa‐Ming |
| description | Objectives
Previously, our investigations demonstrated robust pro‐angiogenic potentials of extracellular vesicles secreted by periodontitis‐compromised dental pulp stem cells (P‐EVs) when compared to those from healthy DPSCs (H‐EVs), but the underlying mechanism remains unknown.
Materials and methods
Here, circulating microRNAs (miRNAs) specifically found in P‐EVs (compared with H‐EVs) were identified by Agilent miRNA microarray analysis, and the roles of the candidate miRNA in P‐EV‐enhanced cell angiogenesis were confirmed by cell transfection and RNA interference methods. Next, the direct binding affinity between the candidate miRNA and its target gene was evaluated by luciferase reporter assay. CCK‐8, transwell/scratch wound healing and tube formation assays were established to investigate the proliferation, migration, and tube formation abilities of endothelial cells (ECs). Western blot was employed to measure the protein levels of Hedgehog/Gli1 signalling pathway components and angiogenesis‐related factors.
Results
The angiogenesis‐related miRNA miR‐378a was found to be enriched in P‐EVs, and its role in P‐EV‐enhanced cell angiogenesis was confirmed, wherein Sufu was identified as a downstream target gene of miR‐378a. Functionally, silencing of Sufu stimulated EC proliferation, migration and tube formation by activating Hedgehog/Gli1 signalling. Further, we found that incubation with P‐EVs enabled the transmission of P‐EV‐contained miR‐378a to ECs. Subsequently, the expressions of Sufu, Gli1 and vascular endothelial growth factor in ECs were significantly influenced by P‐EV‐mediated miR‐378a transmission.
Conclusions
These data suggest that P‐EVs carrying miR‐378a promote EC angiogenesis by downregulating Sufu to activate the Hedgehog/Gli1 signalling pathway. Our findings reveal a crucial role for EV‐derived miR‐378a in cell angiogenesis and hence offer a new target for modifying stem cells and their secreted EVs to enhance vessel regenerative potential.
P‐EVs carrying miR‐378a promote the angiogenesis of ECs by down‐regulating Sufu to activate the Hedgehog/Gli1 signalling pathway. |
| doi_str_mv | 10.1111/cpr.13026 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_8088471</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2504772804</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4716-7c4c9e9791aeed07fcfc9bed4898e740a8d182e28fe6be3f3266f9c162a0e2ee3</originalsourceid><addsrcrecordid>eNp9ks1u1DAUhSMEokNhwQsgS2xgkY5_MrazQapG0CJVUBVYWx7nJuPKiYPtDMyOR-CFeBmeBIcpFSCBN5bs7xzfe32K4jHBJySvpRnDCWGY8jvFgjC-KimR1d1igWuOSyEoPSoexHiNMWFE8PvFEWNiVVNJF8W3SwjWN35INtn4_ctX4_sx-N5GaFADQ9IOjZMbUUzQIwPORRTBBEiA4HMKej6anA5oB9EaBxEZHcLeDh3q7dWb02zJhNRoNvVZ5LzJlnrorO9gyJqINnuUdOggzaJ3Uzuh5JE2ye50FqQtoHNoOtj6bnnmLEHRdoN2LtMPi3utdhEe3ezHxYdXL9-vz8uLt2ev16cXpakE4aUwlamhFjXRAA0WrWlNvYGmkrUEUWEtGyIpUNkC3wBrGeW8rQ3hVGOgAOy4eHHwHadND43JcwnaqTHYXoe98tqqP28Gu1Wd3ymJpcwlZINnNwbBf5wgJpUnPI9OD-CnqOgKV_mjJK4y-vQv9NpPITecKUlXDHNO_k-tKGaYkHp-9vmBMsHHGKC9LZlgNUdH5eion9HJ7JPfe7wlf2UlA8sD8Mk62P_bSa0vrw6WPwDMGtTe</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2520301191</pqid></control><display><type>article</type><title>Periodontitis‐compromised dental pulp stem cells secrete extracellular vesicles carrying miRNA‐378a promote local angiogenesis by targeting Sufu to activate the Hedgehog/Gli1 signalling</title><source>MEDLINE</source><source>Wiley Online Library Open Access</source><source>DOAJ Directory of Open Access Journals</source><source>Wiley Online Library Journals Frontfile Complete</source><source>PubMed Central</source><creator>Zhou, Huan ; Li, Xuan ; Wu, Rui‐Xin ; He, Xiao‐Tao ; An, Ying ; Xu, Xin‐Yue ; Sun, Hai‐Hua ; Wu, Li‐An ; Chen, Fa‐Ming</creator><creatorcontrib>Zhou, Huan ; Li, Xuan ; Wu, Rui‐Xin ; He, Xiao‐Tao ; An, Ying ; Xu, Xin‐Yue ; Sun, Hai‐Hua ; Wu, Li‐An ; Chen, Fa‐Ming</creatorcontrib><description>Objectives
Previously, our investigations demonstrated robust pro‐angiogenic potentials of extracellular vesicles secreted by periodontitis‐compromised dental pulp stem cells (P‐EVs) when compared to those from healthy DPSCs (H‐EVs), but the underlying mechanism remains unknown.
Materials and methods
Here, circulating microRNAs (miRNAs) specifically found in P‐EVs (compared with H‐EVs) were identified by Agilent miRNA microarray analysis, and the roles of the candidate miRNA in P‐EV‐enhanced cell angiogenesis were confirmed by cell transfection and RNA interference methods. Next, the direct binding affinity between the candidate miRNA and its target gene was evaluated by luciferase reporter assay. CCK‐8, transwell/scratch wound healing and tube formation assays were established to investigate the proliferation, migration, and tube formation abilities of endothelial cells (ECs). Western blot was employed to measure the protein levels of Hedgehog/Gli1 signalling pathway components and angiogenesis‐related factors.
Results
The angiogenesis‐related miRNA miR‐378a was found to be enriched in P‐EVs, and its role in P‐EV‐enhanced cell angiogenesis was confirmed, wherein Sufu was identified as a downstream target gene of miR‐378a. Functionally, silencing of Sufu stimulated EC proliferation, migration and tube formation by activating Hedgehog/Gli1 signalling. Further, we found that incubation with P‐EVs enabled the transmission of P‐EV‐contained miR‐378a to ECs. Subsequently, the expressions of Sufu, Gli1 and vascular endothelial growth factor in ECs were significantly influenced by P‐EV‐mediated miR‐378a transmission.
Conclusions
These data suggest that P‐EVs carrying miR‐378a promote EC angiogenesis by downregulating Sufu to activate the Hedgehog/Gli1 signalling pathway. Our findings reveal a crucial role for EV‐derived miR‐378a in cell angiogenesis and hence offer a new target for modifying stem cells and their secreted EVs to enhance vessel regenerative potential.
P‐EVs carrying miR‐378a promote the angiogenesis of ECs by down‐regulating Sufu to activate the Hedgehog/Gli1 signalling pathway.</description><identifier>ISSN: 0960-7722</identifier><identifier>EISSN: 1365-2184</identifier><identifier>DOI: 10.1111/cpr.13026</identifier><identifier>PMID: 33759282</identifier><language>eng</language><publisher>England: John Wiley & Sons, Inc</publisher><subject>Angiogenesis ; Antagomirs - metabolism ; Binding sites ; Cell growth ; Cell Movement - drug effects ; Cell proliferation ; Cell Proliferation - drug effects ; Cholecystokinin ; Dental materials ; Dental pulp ; Dental Pulp - cytology ; Dental Pulp - metabolism ; dental pulp stem cells ; DNA microarrays ; Endothelial cells ; Extracellular vesicles ; Extracellular Vesicles - genetics ; Extracellular Vesicles - metabolism ; Gene expression ; Genes ; Growth factors ; Gum disease ; Hedgehog protein ; Hedgehog Proteins - metabolism ; Human Umbilical Vein Endothelial Cells ; Humans ; Hybridization ; MicroRNAs ; MicroRNAs - antagonists & inhibitors ; MicroRNAs - genetics ; MicroRNAs - metabolism ; miRNA ; Neovascularization, Physiologic ; Original ; Periodontitis ; Periodontitis - metabolism ; Periodontitis - pathology ; Plasmids ; Pyridines - pharmacology ; Pyrimidines - pharmacology ; Repressor Proteins - antagonists & inhibitors ; Repressor Proteins - genetics ; Repressor Proteins - metabolism ; Ribonucleic acid ; RNA ; RNA Interference ; RNA, Small Interfering - metabolism ; RNA-mediated interference ; Signal Transduction ; Signaling ; Stem cells ; Stem Cells - cytology ; Stem Cells - metabolism ; Sufu ; Target recognition ; Teeth ; Tissue engineering ; Transfection ; Vascular endothelial growth factor ; Vesicles ; Wound healing ; Zinc Finger Protein GLI1 - genetics ; Zinc Finger Protein GLI1 - metabolism</subject><ispartof>Cell proliferation, 2021-05, Vol.54 (5), p.e13026-n/a</ispartof><rights>2021 The Authors. published by John Wiley & Sons Ltd.</rights><rights>2021 The Authors. Cell Proliferation published by John Wiley & Sons Ltd.</rights><rights>2021. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4716-7c4c9e9791aeed07fcfc9bed4898e740a8d182e28fe6be3f3266f9c162a0e2ee3</citedby><cites>FETCH-LOGICAL-c4716-7c4c9e9791aeed07fcfc9bed4898e740a8d182e28fe6be3f3266f9c162a0e2ee3</cites><orcidid>0000-0002-8398-2104</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8088471/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8088471/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,1411,11541,27901,27902,45550,45551,46027,46451,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33759282$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhou, Huan</creatorcontrib><creatorcontrib>Li, Xuan</creatorcontrib><creatorcontrib>Wu, Rui‐Xin</creatorcontrib><creatorcontrib>He, Xiao‐Tao</creatorcontrib><creatorcontrib>An, Ying</creatorcontrib><creatorcontrib>Xu, Xin‐Yue</creatorcontrib><creatorcontrib>Sun, Hai‐Hua</creatorcontrib><creatorcontrib>Wu, Li‐An</creatorcontrib><creatorcontrib>Chen, Fa‐Ming</creatorcontrib><title>Periodontitis‐compromised dental pulp stem cells secrete extracellular vesicles carrying miRNA‐378a promote local angiogenesis by targeting Sufu to activate the Hedgehog/Gli1 signalling</title><title>Cell proliferation</title><addtitle>Cell Prolif</addtitle><description>Objectives
Previously, our investigations demonstrated robust pro‐angiogenic potentials of extracellular vesicles secreted by periodontitis‐compromised dental pulp stem cells (P‐EVs) when compared to those from healthy DPSCs (H‐EVs), but the underlying mechanism remains unknown.
Materials and methods
Here, circulating microRNAs (miRNAs) specifically found in P‐EVs (compared with H‐EVs) were identified by Agilent miRNA microarray analysis, and the roles of the candidate miRNA in P‐EV‐enhanced cell angiogenesis were confirmed by cell transfection and RNA interference methods. Next, the direct binding affinity between the candidate miRNA and its target gene was evaluated by luciferase reporter assay. CCK‐8, transwell/scratch wound healing and tube formation assays were established to investigate the proliferation, migration, and tube formation abilities of endothelial cells (ECs). Western blot was employed to measure the protein levels of Hedgehog/Gli1 signalling pathway components and angiogenesis‐related factors.
Results
The angiogenesis‐related miRNA miR‐378a was found to be enriched in P‐EVs, and its role in P‐EV‐enhanced cell angiogenesis was confirmed, wherein Sufu was identified as a downstream target gene of miR‐378a. Functionally, silencing of Sufu stimulated EC proliferation, migration and tube formation by activating Hedgehog/Gli1 signalling. Further, we found that incubation with P‐EVs enabled the transmission of P‐EV‐contained miR‐378a to ECs. Subsequently, the expressions of Sufu, Gli1 and vascular endothelial growth factor in ECs were significantly influenced by P‐EV‐mediated miR‐378a transmission.
Conclusions
These data suggest that P‐EVs carrying miR‐378a promote EC angiogenesis by downregulating Sufu to activate the Hedgehog/Gli1 signalling pathway. Our findings reveal a crucial role for EV‐derived miR‐378a in cell angiogenesis and hence offer a new target for modifying stem cells and their secreted EVs to enhance vessel regenerative potential.
P‐EVs carrying miR‐378a promote the angiogenesis of ECs by down‐regulating Sufu to activate the Hedgehog/Gli1 signalling pathway.</description><subject>Angiogenesis</subject><subject>Antagomirs - metabolism</subject><subject>Binding sites</subject><subject>Cell growth</subject><subject>Cell Movement - drug effects</subject><subject>Cell proliferation</subject><subject>Cell Proliferation - drug effects</subject><subject>Cholecystokinin</subject><subject>Dental materials</subject><subject>Dental pulp</subject><subject>Dental Pulp - cytology</subject><subject>Dental Pulp - metabolism</subject><subject>dental pulp stem cells</subject><subject>DNA microarrays</subject><subject>Endothelial cells</subject><subject>Extracellular vesicles</subject><subject>Extracellular Vesicles - genetics</subject><subject>Extracellular Vesicles - metabolism</subject><subject>Gene expression</subject><subject>Genes</subject><subject>Growth factors</subject><subject>Gum disease</subject><subject>Hedgehog protein</subject><subject>Hedgehog Proteins - metabolism</subject><subject>Human Umbilical Vein Endothelial Cells</subject><subject>Humans</subject><subject>Hybridization</subject><subject>MicroRNAs</subject><subject>MicroRNAs - antagonists & inhibitors</subject><subject>MicroRNAs - genetics</subject><subject>MicroRNAs - metabolism</subject><subject>miRNA</subject><subject>Neovascularization, Physiologic</subject><subject>Original</subject><subject>Periodontitis</subject><subject>Periodontitis - metabolism</subject><subject>Periodontitis - pathology</subject><subject>Plasmids</subject><subject>Pyridines - pharmacology</subject><subject>Pyrimidines - pharmacology</subject><subject>Repressor Proteins - antagonists & inhibitors</subject><subject>Repressor Proteins - genetics</subject><subject>Repressor Proteins - metabolism</subject><subject>Ribonucleic acid</subject><subject>RNA</subject><subject>RNA Interference</subject><subject>RNA, Small Interfering - metabolism</subject><subject>RNA-mediated interference</subject><subject>Signal Transduction</subject><subject>Signaling</subject><subject>Stem cells</subject><subject>Stem Cells - cytology</subject><subject>Stem Cells - metabolism</subject><subject>Sufu</subject><subject>Target recognition</subject><subject>Teeth</subject><subject>Tissue engineering</subject><subject>Transfection</subject><subject>Vascular endothelial growth factor</subject><subject>Vesicles</subject><subject>Wound healing</subject><subject>Zinc Finger Protein GLI1 - genetics</subject><subject>Zinc Finger Protein GLI1 - metabolism</subject><issn>0960-7722</issn><issn>1365-2184</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp9ks1u1DAUhSMEokNhwQsgS2xgkY5_MrazQapG0CJVUBVYWx7nJuPKiYPtDMyOR-CFeBmeBIcpFSCBN5bs7xzfe32K4jHBJySvpRnDCWGY8jvFgjC-KimR1d1igWuOSyEoPSoexHiNMWFE8PvFEWNiVVNJF8W3SwjWN35INtn4_ctX4_sx-N5GaFADQ9IOjZMbUUzQIwPORRTBBEiA4HMKej6anA5oB9EaBxEZHcLeDh3q7dWb02zJhNRoNvVZ5LzJlnrorO9gyJqINnuUdOggzaJ3Uzuh5JE2ye50FqQtoHNoOtj6bnnmLEHRdoN2LtMPi3utdhEe3ezHxYdXL9-vz8uLt2ev16cXpakE4aUwlamhFjXRAA0WrWlNvYGmkrUEUWEtGyIpUNkC3wBrGeW8rQ3hVGOgAOy4eHHwHadND43JcwnaqTHYXoe98tqqP28Gu1Wd3ymJpcwlZINnNwbBf5wgJpUnPI9OD-CnqOgKV_mjJK4y-vQv9NpPITecKUlXDHNO_k-tKGaYkHp-9vmBMsHHGKC9LZlgNUdH5eion9HJ7JPfe7wlf2UlA8sD8Mk62P_bSa0vrw6WPwDMGtTe</recordid><startdate>202105</startdate><enddate>202105</enddate><creator>Zhou, Huan</creator><creator>Li, Xuan</creator><creator>Wu, Rui‐Xin</creator><creator>He, Xiao‐Tao</creator><creator>An, Ying</creator><creator>Xu, Xin‐Yue</creator><creator>Sun, Hai‐Hua</creator><creator>Wu, Li‐An</creator><creator>Chen, Fa‐Ming</creator><general>John Wiley & Sons, Inc</general><general>John Wiley and Sons Inc</general><scope>24P</scope><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>7QO</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>ABUWG</scope><scope>AEUYN</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>GNUQQ</scope><scope>HCIFZ</scope><scope>LK8</scope><scope>M7P</scope><scope>P64</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-8398-2104</orcidid></search><sort><creationdate>202105</creationdate><title>Periodontitis‐compromised dental pulp stem cells secrete extracellular vesicles carrying miRNA‐378a promote local angiogenesis by targeting Sufu to activate the Hedgehog/Gli1 signalling</title><author>Zhou, Huan ; Li, Xuan ; Wu, Rui‐Xin ; He, Xiao‐Tao ; An, Ying ; Xu, Xin‐Yue ; Sun, Hai‐Hua ; Wu, Li‐An ; Chen, Fa‐Ming</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4716-7c4c9e9791aeed07fcfc9bed4898e740a8d182e28fe6be3f3266f9c162a0e2ee3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Angiogenesis</topic><topic>Antagomirs - metabolism</topic><topic>Binding sites</topic><topic>Cell growth</topic><topic>Cell Movement - drug effects</topic><topic>Cell proliferation</topic><topic>Cell Proliferation - drug effects</topic><topic>Cholecystokinin</topic><topic>Dental materials</topic><topic>Dental pulp</topic><topic>Dental Pulp - cytology</topic><topic>Dental Pulp - metabolism</topic><topic>dental pulp stem cells</topic><topic>DNA microarrays</topic><topic>Endothelial cells</topic><topic>Extracellular vesicles</topic><topic>Extracellular Vesicles - genetics</topic><topic>Extracellular Vesicles - metabolism</topic><topic>Gene expression</topic><topic>Genes</topic><topic>Growth factors</topic><topic>Gum disease</topic><topic>Hedgehog protein</topic><topic>Hedgehog Proteins - metabolism</topic><topic>Human Umbilical Vein Endothelial Cells</topic><topic>Humans</topic><topic>Hybridization</topic><topic>MicroRNAs</topic><topic>MicroRNAs - antagonists & inhibitors</topic><topic>MicroRNAs - genetics</topic><topic>MicroRNAs - metabolism</topic><topic>miRNA</topic><topic>Neovascularization, Physiologic</topic><topic>Original</topic><topic>Periodontitis</topic><topic>Periodontitis - metabolism</topic><topic>Periodontitis - pathology</topic><topic>Plasmids</topic><topic>Pyridines - pharmacology</topic><topic>Pyrimidines - pharmacology</topic><topic>Repressor Proteins - antagonists & inhibitors</topic><topic>Repressor Proteins - genetics</topic><topic>Repressor Proteins - metabolism</topic><topic>Ribonucleic acid</topic><topic>RNA</topic><topic>RNA Interference</topic><topic>RNA, Small Interfering - metabolism</topic><topic>RNA-mediated interference</topic><topic>Signal Transduction</topic><topic>Signaling</topic><topic>Stem cells</topic><topic>Stem Cells - cytology</topic><topic>Stem Cells - metabolism</topic><topic>Sufu</topic><topic>Target recognition</topic><topic>Teeth</topic><topic>Tissue engineering</topic><topic>Transfection</topic><topic>Vascular endothelial growth factor</topic><topic>Vesicles</topic><topic>Wound healing</topic><topic>Zinc Finger Protein GLI1 - genetics</topic><topic>Zinc Finger Protein GLI1 - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhou, Huan</creatorcontrib><creatorcontrib>Li, Xuan</creatorcontrib><creatorcontrib>Wu, Rui‐Xin</creatorcontrib><creatorcontrib>He, Xiao‐Tao</creatorcontrib><creatorcontrib>An, Ying</creatorcontrib><creatorcontrib>Xu, Xin‐Yue</creatorcontrib><creatorcontrib>Sun, Hai‐Hua</creatorcontrib><creatorcontrib>Wu, Li‐An</creatorcontrib><creatorcontrib>Chen, Fa‐Ming</creatorcontrib><collection>Wiley Online Library 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>Biotechnology Research Abstracts</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</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>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Biological Science Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cell proliferation</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhou, Huan</au><au>Li, Xuan</au><au>Wu, Rui‐Xin</au><au>He, Xiao‐Tao</au><au>An, Ying</au><au>Xu, Xin‐Yue</au><au>Sun, Hai‐Hua</au><au>Wu, Li‐An</au><au>Chen, Fa‐Ming</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Periodontitis‐compromised dental pulp stem cells secrete extracellular vesicles carrying miRNA‐378a promote local angiogenesis by targeting Sufu to activate the Hedgehog/Gli1 signalling</atitle><jtitle>Cell proliferation</jtitle><addtitle>Cell Prolif</addtitle><date>2021-05</date><risdate>2021</risdate><volume>54</volume><issue>5</issue><spage>e13026</spage><epage>n/a</epage><pages>e13026-n/a</pages><issn>0960-7722</issn><eissn>1365-2184</eissn><abstract>Objectives
Previously, our investigations demonstrated robust pro‐angiogenic potentials of extracellular vesicles secreted by periodontitis‐compromised dental pulp stem cells (P‐EVs) when compared to those from healthy DPSCs (H‐EVs), but the underlying mechanism remains unknown.
Materials and methods
Here, circulating microRNAs (miRNAs) specifically found in P‐EVs (compared with H‐EVs) were identified by Agilent miRNA microarray analysis, and the roles of the candidate miRNA in P‐EV‐enhanced cell angiogenesis were confirmed by cell transfection and RNA interference methods. Next, the direct binding affinity between the candidate miRNA and its target gene was evaluated by luciferase reporter assay. CCK‐8, transwell/scratch wound healing and tube formation assays were established to investigate the proliferation, migration, and tube formation abilities of endothelial cells (ECs). Western blot was employed to measure the protein levels of Hedgehog/Gli1 signalling pathway components and angiogenesis‐related factors.
Results
The angiogenesis‐related miRNA miR‐378a was found to be enriched in P‐EVs, and its role in P‐EV‐enhanced cell angiogenesis was confirmed, wherein Sufu was identified as a downstream target gene of miR‐378a. Functionally, silencing of Sufu stimulated EC proliferation, migration and tube formation by activating Hedgehog/Gli1 signalling. Further, we found that incubation with P‐EVs enabled the transmission of P‐EV‐contained miR‐378a to ECs. Subsequently, the expressions of Sufu, Gli1 and vascular endothelial growth factor in ECs were significantly influenced by P‐EV‐mediated miR‐378a transmission.
Conclusions
These data suggest that P‐EVs carrying miR‐378a promote EC angiogenesis by downregulating Sufu to activate the Hedgehog/Gli1 signalling pathway. Our findings reveal a crucial role for EV‐derived miR‐378a in cell angiogenesis and hence offer a new target for modifying stem cells and their secreted EVs to enhance vessel regenerative potential.
P‐EVs carrying miR‐378a promote the angiogenesis of ECs by down‐regulating Sufu to activate the Hedgehog/Gli1 signalling pathway.</abstract><cop>England</cop><pub>John Wiley & Sons, Inc</pub><pmid>33759282</pmid><doi>10.1111/cpr.13026</doi><tpages>15</tpages><orcidid>https://orcid.org/0000-0002-8398-2104</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | Cell proliferation, 2021-05, Vol.54 (5), p.e13026-n/a |
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| source | MEDLINE; Wiley Online Library Open Access; DOAJ Directory of Open Access Journals; Wiley Online Library Journals Frontfile Complete; PubMed Central |
| subjects | Angiogenesis Antagomirs - metabolism Binding sites Cell growth Cell Movement - drug effects Cell proliferation Cell Proliferation - drug effects Cholecystokinin Dental materials Dental pulp Dental Pulp - cytology Dental Pulp - metabolism dental pulp stem cells DNA microarrays Endothelial cells Extracellular vesicles Extracellular Vesicles - genetics Extracellular Vesicles - metabolism Gene expression Genes Growth factors Gum disease Hedgehog protein Hedgehog Proteins - metabolism Human Umbilical Vein Endothelial Cells Humans Hybridization MicroRNAs MicroRNAs - antagonists & inhibitors MicroRNAs - genetics MicroRNAs - metabolism miRNA Neovascularization, Physiologic Original Periodontitis Periodontitis - metabolism Periodontitis - pathology Plasmids Pyridines - pharmacology Pyrimidines - pharmacology Repressor Proteins - antagonists & inhibitors Repressor Proteins - genetics Repressor Proteins - metabolism Ribonucleic acid RNA RNA Interference RNA, Small Interfering - metabolism RNA-mediated interference Signal Transduction Signaling Stem cells Stem Cells - cytology Stem Cells - metabolism Sufu Target recognition Teeth Tissue engineering Transfection Vascular endothelial growth factor Vesicles Wound healing Zinc Finger Protein GLI1 - genetics Zinc Finger Protein GLI1 - metabolism |
| title | Periodontitis‐compromised dental pulp stem cells secrete extracellular vesicles carrying miRNA‐378a promote local angiogenesis by targeting Sufu to activate the Hedgehog/Gli1 signalling |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-05T16%3A10%3A39IST&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=Periodontitis%E2%80%90compromised%20dental%20pulp%20stem%20cells%20secrete%20extracellular%20vesicles%20carrying%20miRNA%E2%80%90378a%20promote%20local%20angiogenesis%20by%20targeting%20Sufu%20to%20activate%20the%20Hedgehog/Gli1%20signalling&rft.jtitle=Cell%20proliferation&rft.au=Zhou,%20Huan&rft.date=2021-05&rft.volume=54&rft.issue=5&rft.spage=e13026&rft.epage=n/a&rft.pages=e13026-n/a&rft.issn=0960-7722&rft.eissn=1365-2184&rft_id=info:doi/10.1111/cpr.13026&rft_dat=%3Cproquest_pubme%3E2504772804%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=2520301191&rft_id=info:pmid/33759282&rfr_iscdi=true |