SHED‐exos promote saliva secretion by suppressing p‐ERK1/2‐mediated apoptosis in glandular cells
Objectives Confirm that stem cells from human exfoliated deciduous teeth‐derived exosomes (SHED‐exos) can limit inflammation‐triggered epithelial cell apoptosis and explore the molecular mechanism. Methods SHED‐exos were injected into the submandibular glands (SMGs) of non‐obese diabetic (NOD) mice,...
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| Veröffentlicht in: | Oral diseases 2024-07, Vol.30 (5), p.3066-3080 |
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| creator | Chu, Wei‐Xia Ding, Chong Du, Zhi‐Hao Wei, Pan Wang, Yi‐Xiang Ge, Xue‐Jun Yu, Guang‐Yan |
| description | Objectives
Confirm that stem cells from human exfoliated deciduous teeth‐derived exosomes (SHED‐exos) can limit inflammation‐triggered epithelial cell apoptosis and explore the molecular mechanism.
Methods
SHED‐exos were injected into the submandibular glands (SMGs) of non‐obese diabetic (NOD) mice, an animal model of Sjögren's syndrome (SS). Cell death was evaluated by western blotting and terminal deoxynucleotidyl transferase‐mediated dUTP nick‐end labelling staining.
Results
SHED‐exos treatment promoted the saliva flow rates of NOD mice, accompanied by decreased cleaved caspase‐3 levels and apoptotic cell numbers in SMGs. SHED‐exos inhibited autophagy, pyroptosis, NETosis, ferroptosis, necroptosis and oxeiptosis marker expression in SS‐damaged glands. Mechanistically, Kyoto Encyclopedia of Genes and Genomes analysis of exosomal miRNAs suggested that the rat sarcoma virus (RAS)/mitogen‐activated protein kinase kinase (MEK)/extracellular signal‐regulated kinase (ERK) pathway might play an important role. In vivo, the expression of Kirsten RAS, Harvey RAS, MEK1/2 and p‐ERK1/2 was upregulated in SMGs, and this change was blocked by SHED‐exos treatment. In vitro, SHED‐exos suppressed p‐ERK1/2 activation and increased cleaved caspase‐3 and apoptotic cell numbers, which were induced by IFN‐γ.
Conclusion
SHED‐exos suppress epithelial cell death, which is responsible for promoting salivary secretion. SHED‐exos inhibited inflammation‐triggered epithelial cell apoptosis by suppressing p‐ERK1/2 activation, which is involved in these effects. |
| doi_str_mv | 10.1111/odi.14776 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_2878713575</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>3082766681</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3886-8c5fbee7cf2ed5e893ce521f3a7d0cf38008d72c2586163cf03ede2d7b77b84f3</originalsourceid><addsrcrecordid>eNp1kM1O3DAQxy3UCijlwAsgS720h7D-SGLvEcFSUJGQ-iH1Zjn2GBll4-BJ2u6NR-gz9klqutBDpc5l5vCbv2Z-hBxxdsJLLZKPJ7xWqt0h-7xlvGJaNC_KLJu6aoT8ukdeId4xxtVSil2yJ5Wul3Wt9kn4dLk6__XwE34kpGNO6zQBRdvHb5YiuAxTTAPtNhTnccyAGIdbOpaF1ccPfCHKsAYf7QSe2jGNU8KINA70treDn3ubqYO-x9fkZbA9wuFTPyBfLlafzy6r65v3V2en15WTWreVdk3oAJQLAnwDeikdNIIHaZVnLkjNmPZKONHolrfSBSbBg_CqU6rTdZAH5O02t7xyPwNOZh3x8QI7QJrRCK20KlpUU9A3_6B3ac5Duc7I4k-1bat5od5tKZcTYoZgxhzXNm8MZ-ZRvinyzR_5hT1-Spy7YuUv-Wy7AIst8D32sPl_krk5v9pG_gZJspFj</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>3082766681</pqid></control><display><type>article</type><title>SHED‐exos promote saliva secretion by suppressing p‐ERK1/2‐mediated apoptosis in glandular cells</title><source>MEDLINE</source><source>Wiley Online Library Journals Frontfile Complete</source><creator>Chu, Wei‐Xia ; Ding, Chong ; Du, Zhi‐Hao ; Wei, Pan ; Wang, Yi‐Xiang ; Ge, Xue‐Jun ; Yu, Guang‐Yan</creator><creatorcontrib>Chu, Wei‐Xia ; Ding, Chong ; Du, Zhi‐Hao ; Wei, Pan ; Wang, Yi‐Xiang ; Ge, Xue‐Jun ; Yu, Guang‐Yan</creatorcontrib><description>Objectives
Confirm that stem cells from human exfoliated deciduous teeth‐derived exosomes (SHED‐exos) can limit inflammation‐triggered epithelial cell apoptosis and explore the molecular mechanism.
Methods
SHED‐exos were injected into the submandibular glands (SMGs) of non‐obese diabetic (NOD) mice, an animal model of Sjögren's syndrome (SS). Cell death was evaluated by western blotting and terminal deoxynucleotidyl transferase‐mediated dUTP nick‐end labelling staining.
Results
SHED‐exos treatment promoted the saliva flow rates of NOD mice, accompanied by decreased cleaved caspase‐3 levels and apoptotic cell numbers in SMGs. SHED‐exos inhibited autophagy, pyroptosis, NETosis, ferroptosis, necroptosis and oxeiptosis marker expression in SS‐damaged glands. Mechanistically, Kyoto Encyclopedia of Genes and Genomes analysis of exosomal miRNAs suggested that the rat sarcoma virus (RAS)/mitogen‐activated protein kinase kinase (MEK)/extracellular signal‐regulated kinase (ERK) pathway might play an important role. In vivo, the expression of Kirsten RAS, Harvey RAS, MEK1/2 and p‐ERK1/2 was upregulated in SMGs, and this change was blocked by SHED‐exos treatment. In vitro, SHED‐exos suppressed p‐ERK1/2 activation and increased cleaved caspase‐3 and apoptotic cell numbers, which were induced by IFN‐γ.
Conclusion
SHED‐exos suppress epithelial cell death, which is responsible for promoting salivary secretion. SHED‐exos inhibited inflammation‐triggered epithelial cell apoptosis by suppressing p‐ERK1/2 activation, which is involved in these effects.</description><identifier>ISSN: 1354-523X</identifier><identifier>ISSN: 1601-0825</identifier><identifier>EISSN: 1601-0825</identifier><identifier>DOI: 10.1111/odi.14776</identifier><identifier>PMID: 37849447</identifier><language>eng</language><publisher>Denmark: Wiley Subscription Services, Inc</publisher><subject>Animal models ; Animals ; Apoptosis ; Autophagy ; Caspase ; Cell activation ; Cell death ; Diabetes mellitus ; Disease Models, Animal ; DNA nucleotidylexotransferase ; Epithelial cells ; Epithelial Cells - metabolism ; Exosomes ; Exosomes - metabolism ; Extracellular signal-regulated kinase ; Female ; Ferroptosis ; Humans ; Inflammation ; Kinases ; Labeling ; MAP Kinase Signaling System ; Mice ; Mice, Inbred NOD ; MicroRNAs - metabolism ; Mitogen-Activated Protein Kinase 3 - metabolism ; Molecular modelling ; Necroptosis ; Pyroptosis ; Saliva ; Saliva - metabolism ; Salivation ; Sarcoma ; Secretion ; Sjogren's syndrome ; Sjogren's Syndrome - metabolism ; Sjögren's syndrome ; Stem Cells - metabolism ; Submandibular Gland - metabolism ; Western blotting</subject><ispartof>Oral diseases, 2024-07, Vol.30 (5), p.3066-3080</ispartof><rights>2023 The Authors. published by Wiley Periodicals LLC.</rights><rights>2023 The Authors. Oral Diseases published by Wiley Periodicals LLC.</rights><rights>2023. This article is published under http://creativecommons.org/licenses/by-nc-nd/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-c3886-8c5fbee7cf2ed5e893ce521f3a7d0cf38008d72c2586163cf03ede2d7b77b84f3</citedby><cites>FETCH-LOGICAL-c3886-8c5fbee7cf2ed5e893ce521f3a7d0cf38008d72c2586163cf03ede2d7b77b84f3</cites><orcidid>0000-0002-1834-4421</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fodi.14776$$EPDF$$P50$$Gwiley$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fodi.14776$$EHTML$$P50$$Gwiley$$Hfree_for_read</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37849447$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chu, Wei‐Xia</creatorcontrib><creatorcontrib>Ding, Chong</creatorcontrib><creatorcontrib>Du, Zhi‐Hao</creatorcontrib><creatorcontrib>Wei, Pan</creatorcontrib><creatorcontrib>Wang, Yi‐Xiang</creatorcontrib><creatorcontrib>Ge, Xue‐Jun</creatorcontrib><creatorcontrib>Yu, Guang‐Yan</creatorcontrib><title>SHED‐exos promote saliva secretion by suppressing p‐ERK1/2‐mediated apoptosis in glandular cells</title><title>Oral diseases</title><addtitle>Oral Dis</addtitle><description>Objectives
Confirm that stem cells from human exfoliated deciduous teeth‐derived exosomes (SHED‐exos) can limit inflammation‐triggered epithelial cell apoptosis and explore the molecular mechanism.
Methods
SHED‐exos were injected into the submandibular glands (SMGs) of non‐obese diabetic (NOD) mice, an animal model of Sjögren's syndrome (SS). Cell death was evaluated by western blotting and terminal deoxynucleotidyl transferase‐mediated dUTP nick‐end labelling staining.
Results
SHED‐exos treatment promoted the saliva flow rates of NOD mice, accompanied by decreased cleaved caspase‐3 levels and apoptotic cell numbers in SMGs. SHED‐exos inhibited autophagy, pyroptosis, NETosis, ferroptosis, necroptosis and oxeiptosis marker expression in SS‐damaged glands. Mechanistically, Kyoto Encyclopedia of Genes and Genomes analysis of exosomal miRNAs suggested that the rat sarcoma virus (RAS)/mitogen‐activated protein kinase kinase (MEK)/extracellular signal‐regulated kinase (ERK) pathway might play an important role. In vivo, the expression of Kirsten RAS, Harvey RAS, MEK1/2 and p‐ERK1/2 was upregulated in SMGs, and this change was blocked by SHED‐exos treatment. In vitro, SHED‐exos suppressed p‐ERK1/2 activation and increased cleaved caspase‐3 and apoptotic cell numbers, which were induced by IFN‐γ.
Conclusion
SHED‐exos suppress epithelial cell death, which is responsible for promoting salivary secretion. SHED‐exos inhibited inflammation‐triggered epithelial cell apoptosis by suppressing p‐ERK1/2 activation, which is involved in these effects.</description><subject>Animal models</subject><subject>Animals</subject><subject>Apoptosis</subject><subject>Autophagy</subject><subject>Caspase</subject><subject>Cell activation</subject><subject>Cell death</subject><subject>Diabetes mellitus</subject><subject>Disease Models, Animal</subject><subject>DNA nucleotidylexotransferase</subject><subject>Epithelial cells</subject><subject>Epithelial Cells - metabolism</subject><subject>Exosomes</subject><subject>Exosomes - metabolism</subject><subject>Extracellular signal-regulated kinase</subject><subject>Female</subject><subject>Ferroptosis</subject><subject>Humans</subject><subject>Inflammation</subject><subject>Kinases</subject><subject>Labeling</subject><subject>MAP Kinase Signaling System</subject><subject>Mice</subject><subject>Mice, Inbred NOD</subject><subject>MicroRNAs - metabolism</subject><subject>Mitogen-Activated Protein Kinase 3 - metabolism</subject><subject>Molecular modelling</subject><subject>Necroptosis</subject><subject>Pyroptosis</subject><subject>Saliva</subject><subject>Saliva - metabolism</subject><subject>Salivation</subject><subject>Sarcoma</subject><subject>Secretion</subject><subject>Sjogren's syndrome</subject><subject>Sjogren's Syndrome - metabolism</subject><subject>Sjögren's syndrome</subject><subject>Stem Cells - metabolism</subject><subject>Submandibular Gland - metabolism</subject><subject>Western blotting</subject><issn>1354-523X</issn><issn>1601-0825</issn><issn>1601-0825</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>EIF</sourceid><recordid>eNp1kM1O3DAQxy3UCijlwAsgS720h7D-SGLvEcFSUJGQ-iH1Zjn2GBll4-BJ2u6NR-gz9klqutBDpc5l5vCbv2Z-hBxxdsJLLZKPJ7xWqt0h-7xlvGJaNC_KLJu6aoT8ukdeId4xxtVSil2yJ5Wul3Wt9kn4dLk6__XwE34kpGNO6zQBRdvHb5YiuAxTTAPtNhTnccyAGIdbOpaF1ccPfCHKsAYf7QSe2jGNU8KINA70treDn3ubqYO-x9fkZbA9wuFTPyBfLlafzy6r65v3V2en15WTWreVdk3oAJQLAnwDeikdNIIHaZVnLkjNmPZKONHolrfSBSbBg_CqU6rTdZAH5O02t7xyPwNOZh3x8QI7QJrRCK20KlpUU9A3_6B3ac5Duc7I4k-1bat5od5tKZcTYoZgxhzXNm8MZ-ZRvinyzR_5hT1-Spy7YuUv-Wy7AIst8D32sPl_krk5v9pG_gZJspFj</recordid><startdate>202407</startdate><enddate>202407</enddate><creator>Chu, Wei‐Xia</creator><creator>Ding, Chong</creator><creator>Du, Zhi‐Hao</creator><creator>Wei, Pan</creator><creator>Wang, Yi‐Xiang</creator><creator>Ge, Xue‐Jun</creator><creator>Yu, Guang‐Yan</creator><general>Wiley Subscription Services, 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>7QP</scope><scope>K9.</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-1834-4421</orcidid></search><sort><creationdate>202407</creationdate><title>SHED‐exos promote saliva secretion by suppressing p‐ERK1/2‐mediated apoptosis in glandular cells</title><author>Chu, Wei‐Xia ; Ding, Chong ; Du, Zhi‐Hao ; Wei, Pan ; Wang, Yi‐Xiang ; Ge, Xue‐Jun ; Yu, Guang‐Yan</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3886-8c5fbee7cf2ed5e893ce521f3a7d0cf38008d72c2586163cf03ede2d7b77b84f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Animal models</topic><topic>Animals</topic><topic>Apoptosis</topic><topic>Autophagy</topic><topic>Caspase</topic><topic>Cell activation</topic><topic>Cell death</topic><topic>Diabetes mellitus</topic><topic>Disease Models, Animal</topic><topic>DNA nucleotidylexotransferase</topic><topic>Epithelial cells</topic><topic>Epithelial Cells - metabolism</topic><topic>Exosomes</topic><topic>Exosomes - metabolism</topic><topic>Extracellular signal-regulated kinase</topic><topic>Female</topic><topic>Ferroptosis</topic><topic>Humans</topic><topic>Inflammation</topic><topic>Kinases</topic><topic>Labeling</topic><topic>MAP Kinase Signaling System</topic><topic>Mice</topic><topic>Mice, Inbred NOD</topic><topic>MicroRNAs - metabolism</topic><topic>Mitogen-Activated Protein Kinase 3 - metabolism</topic><topic>Molecular modelling</topic><topic>Necroptosis</topic><topic>Pyroptosis</topic><topic>Saliva</topic><topic>Saliva - metabolism</topic><topic>Salivation</topic><topic>Sarcoma</topic><topic>Secretion</topic><topic>Sjogren's syndrome</topic><topic>Sjogren's Syndrome - metabolism</topic><topic>Sjögren's syndrome</topic><topic>Stem Cells - metabolism</topic><topic>Submandibular Gland - metabolism</topic><topic>Western blotting</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chu, Wei‐Xia</creatorcontrib><creatorcontrib>Ding, Chong</creatorcontrib><creatorcontrib>Du, Zhi‐Hao</creatorcontrib><creatorcontrib>Wei, Pan</creatorcontrib><creatorcontrib>Wang, Yi‐Xiang</creatorcontrib><creatorcontrib>Ge, Xue‐Jun</creatorcontrib><creatorcontrib>Yu, Guang‐Yan</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>Calcium & Calcified Tissue Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>Oral diseases</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chu, Wei‐Xia</au><au>Ding, Chong</au><au>Du, Zhi‐Hao</au><au>Wei, Pan</au><au>Wang, Yi‐Xiang</au><au>Ge, Xue‐Jun</au><au>Yu, Guang‐Yan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>SHED‐exos promote saliva secretion by suppressing p‐ERK1/2‐mediated apoptosis in glandular cells</atitle><jtitle>Oral diseases</jtitle><addtitle>Oral Dis</addtitle><date>2024-07</date><risdate>2024</risdate><volume>30</volume><issue>5</issue><spage>3066</spage><epage>3080</epage><pages>3066-3080</pages><issn>1354-523X</issn><issn>1601-0825</issn><eissn>1601-0825</eissn><abstract>Objectives
Confirm that stem cells from human exfoliated deciduous teeth‐derived exosomes (SHED‐exos) can limit inflammation‐triggered epithelial cell apoptosis and explore the molecular mechanism.
Methods
SHED‐exos were injected into the submandibular glands (SMGs) of non‐obese diabetic (NOD) mice, an animal model of Sjögren's syndrome (SS). Cell death was evaluated by western blotting and terminal deoxynucleotidyl transferase‐mediated dUTP nick‐end labelling staining.
Results
SHED‐exos treatment promoted the saliva flow rates of NOD mice, accompanied by decreased cleaved caspase‐3 levels and apoptotic cell numbers in SMGs. SHED‐exos inhibited autophagy, pyroptosis, NETosis, ferroptosis, necroptosis and oxeiptosis marker expression in SS‐damaged glands. Mechanistically, Kyoto Encyclopedia of Genes and Genomes analysis of exosomal miRNAs suggested that the rat sarcoma virus (RAS)/mitogen‐activated protein kinase kinase (MEK)/extracellular signal‐regulated kinase (ERK) pathway might play an important role. In vivo, the expression of Kirsten RAS, Harvey RAS, MEK1/2 and p‐ERK1/2 was upregulated in SMGs, and this change was blocked by SHED‐exos treatment. In vitro, SHED‐exos suppressed p‐ERK1/2 activation and increased cleaved caspase‐3 and apoptotic cell numbers, which were induced by IFN‐γ.
Conclusion
SHED‐exos suppress epithelial cell death, which is responsible for promoting salivary secretion. SHED‐exos inhibited inflammation‐triggered epithelial cell apoptosis by suppressing p‐ERK1/2 activation, which is involved in these effects.</abstract><cop>Denmark</cop><pub>Wiley Subscription Services, Inc</pub><pmid>37849447</pmid><doi>10.1111/odi.14776</doi><tpages>15</tpages><orcidid>https://orcid.org/0000-0002-1834-4421</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Animal models Animals Apoptosis Autophagy Caspase Cell activation Cell death Diabetes mellitus Disease Models, Animal DNA nucleotidylexotransferase Epithelial cells Epithelial Cells - metabolism Exosomes Exosomes - metabolism Extracellular signal-regulated kinase Female Ferroptosis Humans Inflammation Kinases Labeling MAP Kinase Signaling System Mice Mice, Inbred NOD MicroRNAs - metabolism Mitogen-Activated Protein Kinase 3 - metabolism Molecular modelling Necroptosis Pyroptosis Saliva Saliva - metabolism Salivation Sarcoma Secretion Sjogren's syndrome Sjogren's Syndrome - metabolism Sjögren's syndrome Stem Cells - metabolism Submandibular Gland - metabolism Western blotting |
| title | SHED‐exos promote saliva secretion by suppressing p‐ERK1/2‐mediated apoptosis in glandular cells |
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