Milk-derived exosomes carrying siRNA-KEAP1 promote diabetic wound healing by improving oxidative stress
Diabetic wounds are a serious complication of diabetes mellitus (DM) that can lead to persistent infection, amputation, and even death. Prolonged oxidative stress has been widely recognized as a major instigator in the development of diabetic wounds; therefore, oxidative stress is considered a promi...
Gespeichert in:
| Veröffentlicht in: | Drug delivery and translational research 2023-09, Vol.13 (9), p.2286-2296 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 2296 |
|---|---|
| container_issue | 9 |
| container_start_page | 2286 |
| container_title | Drug delivery and translational research |
| container_volume | 13 |
| creator | Xiang, Xuejiao Chen, Jing Jiang, Tao Yan, Chengqi Kang, Yu Zhang, Maojie Xiang, Kaituo Guo, Jiahe Jiang, Guoyong Wang, Cheng XiangXu Yang, Xiaofan Chen, Zhenbing |
| description | Diabetic wounds are a serious complication of diabetes mellitus (DM) that can lead to persistent infection, amputation, and even death. Prolonged oxidative stress has been widely recognized as a major instigator in the development of diabetic wounds; therefore, oxidative stress is considered a promising therapeutic target. In the present study, Keap1/Nrf2 signaling was confirmed to be activated in streptozotocin (STZ)-induced diabetic mice and methylglyoxal (MGO)-treated human umbilical vein endothelial cells (HUVECs). Knockdown of Keap1 by siRNA reversed the increase in Keap1 levels, promoted the nuclear translocation of Nrf2, and increased the expression of HO-1, an antioxidant protein. To explore therapeutic delivery strategies, milk-derived exosomes (mEXOs) were developed as a novel, efficient, and non-toxic siRNA carrier. SiRNA-Keap1 (siKeap1) was loaded into mEXOs by sonication, and the obtained mEXOs-siKeap1 were found to promote HUVEC proliferation and migration while relieving oxidative stress in MGO-treated HUVECs. Meanwhile, in a mouse model of diabetic wounds, injection of mEXOs-siKeap1 significantly accelerated diabetic wound healing with enhanced collagen formation and neovascularization. Taken together, these data support the development of Keap1 knockdown as a potential therapeutic strategy for diabetic wounds and demonstrated the feasibility of mEXOs as a scalable, biocompatible, and cost-effective siRNA delivery system.
Graphical Abstract
The therapeutic effect of siKeap1-loaded mEXOs on diabetic wound healing was assessed. First, we found that the expression of Keap1 was upregulated in the wounds of diabetic mice and in human umbilical vein endothelial cells (HUVECs) pretreated with methylglyoxal (MGO). Next, we extracted exosomes from raw milk by differential centrifugation and loaded siKeap1 into milk-derived exosomes by sonication. The in vitro application of the synthetic complex (mEXOs-siKeap1) was found to increase the nuclear localization of Nrf2 and the expression of the antioxidant protein HO-1, thus reversing oxidative stress. Furthermore, in vivo mEXOs-siKeap1 administration significantly accelerated the healing rate of diabetic wounds (Scheme 1).
Scheme 1
Schematic diagram.
A
Synthesis of mEXOs-siKeap1 complex.
B
Mechanism of mEXOs-siKeap1 in vitro.
C
The treatment effect of mEXOs-siKeap1 on an in vivo mouse model of diabetic wounds |
| doi_str_mv | 10.1007/s13346-023-01306-x |
| format | Article |
| fullrecord | <record><control><sourceid>pubmed_cross</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_9904251</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>36749479</sourcerecordid><originalsourceid>FETCH-LOGICAL-c446t-9dca53a567cd64df9c2c334c8aee083a6f762f683119fee39d1ea1ed0afe99843</originalsourceid><addsrcrecordid>eNp9kM1OAyEYRYnRqKm-gAvDC6AwUGbYmDTGv_gbo4k7QuGbinaGBqa1fXup1UY3sgHy3XsIB6EDRo8YpeVxYpwLSWjBCWWcSjLfQLsFU5RwJarN9Zm_7KD9lN5oXkKyUpXbaIfLUihRql00uvXjd-Ig-hk4DPOQQgMJWxPjwrcjnPzj3YBcnw0eGJ7E0IQOsPNmCJ23-CNMW4dfwYyX0eEC-yZnZstLmHtnugzFqYuQ0h7aqs04wf733kPP52dPp5fk5v7i6nRwQ6wQsiPKWdPnpi9L66RwtbKFzf-0lQGgFTeyLmVRy4ozpmoArhwDw8BRU4NSleA9dLLiTqbDBpyFtotmrCfRNyYudDBe_520_lWPwkwrRUXRZxlQrAA2hpQi1Osuo3ppXq_M62xef5nX81w6_P3quvLjOQf4KpDyqB1B1G9hGtts4j_sJ62lkww</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>Milk-derived exosomes carrying siRNA-KEAP1 promote diabetic wound healing by improving oxidative stress</title><source>MEDLINE</source><source>SpringerLink Journals - AutoHoldings</source><creator>Xiang, Xuejiao ; Chen, Jing ; Jiang, Tao ; Yan, Chengqi ; Kang, Yu ; Zhang, Maojie ; Xiang, Kaituo ; Guo, Jiahe ; Jiang, Guoyong ; Wang, Cheng ; XiangXu ; Yang, Xiaofan ; Chen, Zhenbing</creator><creatorcontrib>Xiang, Xuejiao ; Chen, Jing ; Jiang, Tao ; Yan, Chengqi ; Kang, Yu ; Zhang, Maojie ; Xiang, Kaituo ; Guo, Jiahe ; Jiang, Guoyong ; Wang, Cheng ; XiangXu ; Yang, Xiaofan ; Chen, Zhenbing</creatorcontrib><description>Diabetic wounds are a serious complication of diabetes mellitus (DM) that can lead to persistent infection, amputation, and even death. Prolonged oxidative stress has been widely recognized as a major instigator in the development of diabetic wounds; therefore, oxidative stress is considered a promising therapeutic target. In the present study, Keap1/Nrf2 signaling was confirmed to be activated in streptozotocin (STZ)-induced diabetic mice and methylglyoxal (MGO)-treated human umbilical vein endothelial cells (HUVECs). Knockdown of Keap1 by siRNA reversed the increase in Keap1 levels, promoted the nuclear translocation of Nrf2, and increased the expression of HO-1, an antioxidant protein. To explore therapeutic delivery strategies, milk-derived exosomes (mEXOs) were developed as a novel, efficient, and non-toxic siRNA carrier. SiRNA-Keap1 (siKeap1) was loaded into mEXOs by sonication, and the obtained mEXOs-siKeap1 were found to promote HUVEC proliferation and migration while relieving oxidative stress in MGO-treated HUVECs. Meanwhile, in a mouse model of diabetic wounds, injection of mEXOs-siKeap1 significantly accelerated diabetic wound healing with enhanced collagen formation and neovascularization. Taken together, these data support the development of Keap1 knockdown as a potential therapeutic strategy for diabetic wounds and demonstrated the feasibility of mEXOs as a scalable, biocompatible, and cost-effective siRNA delivery system.
Graphical Abstract
The therapeutic effect of siKeap1-loaded mEXOs on diabetic wound healing was assessed. First, we found that the expression of Keap1 was upregulated in the wounds of diabetic mice and in human umbilical vein endothelial cells (HUVECs) pretreated with methylglyoxal (MGO). Next, we extracted exosomes from raw milk by differential centrifugation and loaded siKeap1 into milk-derived exosomes by sonication. The in vitro application of the synthetic complex (mEXOs-siKeap1) was found to increase the nuclear localization of Nrf2 and the expression of the antioxidant protein HO-1, thus reversing oxidative stress. Furthermore, in vivo mEXOs-siKeap1 administration significantly accelerated the healing rate of diabetic wounds (Scheme 1).
Scheme 1
Schematic diagram.
A
Synthesis of mEXOs-siKeap1 complex.
B
Mechanism of mEXOs-siKeap1 in vitro.
C
The treatment effect of mEXOs-siKeap1 on an in vivo mouse model of diabetic wounds</description><identifier>ISSN: 2190-393X</identifier><identifier>EISSN: 2190-3948</identifier><identifier>DOI: 10.1007/s13346-023-01306-x</identifier><identifier>PMID: 36749479</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>Animals ; Antioxidants - pharmacology ; Biomedical and Life Sciences ; Biomedicine ; Diabetes Mellitus, Experimental - drug therapy ; Exosomes - metabolism ; Human Umbilical Vein Endothelial Cells - metabolism ; Humans ; Kelch-Like ECH-Associated Protein 1 - metabolism ; Magnesium Oxide - metabolism ; Magnesium Oxide - pharmacology ; Magnesium Oxide - therapeutic use ; Mice ; Milk - metabolism ; NF-E2-Related Factor 2 - genetics ; NF-E2-Related Factor 2 - metabolism ; NF-E2-Related Factor 2 - pharmacology ; Original ; Original Article ; Oxidative Stress ; Pharmaceutical Sciences/Technology ; Pyruvaldehyde - metabolism ; Pyruvaldehyde - pharmacology ; Pyruvaldehyde - therapeutic use ; RNA, Small Interfering - pharmacology ; Wound Healing</subject><ispartof>Drug delivery and translational research, 2023-09, Vol.13 (9), p.2286-2296</ispartof><rights>Controlled Release Society 2023. 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>2023. Controlled Release Society.</rights><rights>Controlled Release Society 2023, 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-c446t-9dca53a567cd64df9c2c334c8aee083a6f762f683119fee39d1ea1ed0afe99843</citedby><cites>FETCH-LOGICAL-c446t-9dca53a567cd64df9c2c334c8aee083a6f762f683119fee39d1ea1ed0afe99843</cites><orcidid>0000-0003-2828-866X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s13346-023-01306-x$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s13346-023-01306-x$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>230,314,780,784,885,27922,27923,41486,42555,51317</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36749479$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Xiang, Xuejiao</creatorcontrib><creatorcontrib>Chen, Jing</creatorcontrib><creatorcontrib>Jiang, Tao</creatorcontrib><creatorcontrib>Yan, Chengqi</creatorcontrib><creatorcontrib>Kang, Yu</creatorcontrib><creatorcontrib>Zhang, Maojie</creatorcontrib><creatorcontrib>Xiang, Kaituo</creatorcontrib><creatorcontrib>Guo, Jiahe</creatorcontrib><creatorcontrib>Jiang, Guoyong</creatorcontrib><creatorcontrib>Wang, Cheng</creatorcontrib><creatorcontrib>XiangXu</creatorcontrib><creatorcontrib>Yang, Xiaofan</creatorcontrib><creatorcontrib>Chen, Zhenbing</creatorcontrib><title>Milk-derived exosomes carrying siRNA-KEAP1 promote diabetic wound healing by improving oxidative stress</title><title>Drug delivery and translational research</title><addtitle>Drug Deliv. and Transl. Res</addtitle><addtitle>Drug Deliv Transl Res</addtitle><description>Diabetic wounds are a serious complication of diabetes mellitus (DM) that can lead to persistent infection, amputation, and even death. Prolonged oxidative stress has been widely recognized as a major instigator in the development of diabetic wounds; therefore, oxidative stress is considered a promising therapeutic target. In the present study, Keap1/Nrf2 signaling was confirmed to be activated in streptozotocin (STZ)-induced diabetic mice and methylglyoxal (MGO)-treated human umbilical vein endothelial cells (HUVECs). Knockdown of Keap1 by siRNA reversed the increase in Keap1 levels, promoted the nuclear translocation of Nrf2, and increased the expression of HO-1, an antioxidant protein. To explore therapeutic delivery strategies, milk-derived exosomes (mEXOs) were developed as a novel, efficient, and non-toxic siRNA carrier. SiRNA-Keap1 (siKeap1) was loaded into mEXOs by sonication, and the obtained mEXOs-siKeap1 were found to promote HUVEC proliferation and migration while relieving oxidative stress in MGO-treated HUVECs. Meanwhile, in a mouse model of diabetic wounds, injection of mEXOs-siKeap1 significantly accelerated diabetic wound healing with enhanced collagen formation and neovascularization. Taken together, these data support the development of Keap1 knockdown as a potential therapeutic strategy for diabetic wounds and demonstrated the feasibility of mEXOs as a scalable, biocompatible, and cost-effective siRNA delivery system.
Graphical Abstract
The therapeutic effect of siKeap1-loaded mEXOs on diabetic wound healing was assessed. First, we found that the expression of Keap1 was upregulated in the wounds of diabetic mice and in human umbilical vein endothelial cells (HUVECs) pretreated with methylglyoxal (MGO). Next, we extracted exosomes from raw milk by differential centrifugation and loaded siKeap1 into milk-derived exosomes by sonication. The in vitro application of the synthetic complex (mEXOs-siKeap1) was found to increase the nuclear localization of Nrf2 and the expression of the antioxidant protein HO-1, thus reversing oxidative stress. Furthermore, in vivo mEXOs-siKeap1 administration significantly accelerated the healing rate of diabetic wounds (Scheme 1).
Scheme 1
Schematic diagram.
A
Synthesis of mEXOs-siKeap1 complex.
B
Mechanism of mEXOs-siKeap1 in vitro.
C
The treatment effect of mEXOs-siKeap1 on an in vivo mouse model of diabetic wounds</description><subject>Animals</subject><subject>Antioxidants - pharmacology</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Diabetes Mellitus, Experimental - drug therapy</subject><subject>Exosomes - metabolism</subject><subject>Human Umbilical Vein Endothelial Cells - metabolism</subject><subject>Humans</subject><subject>Kelch-Like ECH-Associated Protein 1 - metabolism</subject><subject>Magnesium Oxide - metabolism</subject><subject>Magnesium Oxide - pharmacology</subject><subject>Magnesium Oxide - therapeutic use</subject><subject>Mice</subject><subject>Milk - metabolism</subject><subject>NF-E2-Related Factor 2 - genetics</subject><subject>NF-E2-Related Factor 2 - metabolism</subject><subject>NF-E2-Related Factor 2 - pharmacology</subject><subject>Original</subject><subject>Original Article</subject><subject>Oxidative Stress</subject><subject>Pharmaceutical Sciences/Technology</subject><subject>Pyruvaldehyde - metabolism</subject><subject>Pyruvaldehyde - pharmacology</subject><subject>Pyruvaldehyde - therapeutic use</subject><subject>RNA, Small Interfering - pharmacology</subject><subject>Wound Healing</subject><issn>2190-393X</issn><issn>2190-3948</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kM1OAyEYRYnRqKm-gAvDC6AwUGbYmDTGv_gbo4k7QuGbinaGBqa1fXup1UY3sgHy3XsIB6EDRo8YpeVxYpwLSWjBCWWcSjLfQLsFU5RwJarN9Zm_7KD9lN5oXkKyUpXbaIfLUihRql00uvXjd-Ig-hk4DPOQQgMJWxPjwrcjnPzj3YBcnw0eGJ7E0IQOsPNmCJ23-CNMW4dfwYyX0eEC-yZnZstLmHtnugzFqYuQ0h7aqs04wf733kPP52dPp5fk5v7i6nRwQ6wQsiPKWdPnpi9L66RwtbKFzf-0lQGgFTeyLmVRy4ozpmoArhwDw8BRU4NSleA9dLLiTqbDBpyFtotmrCfRNyYudDBe_520_lWPwkwrRUXRZxlQrAA2hpQi1Osuo3ppXq_M62xef5nX81w6_P3quvLjOQf4KpDyqB1B1G9hGtts4j_sJ62lkww</recordid><startdate>20230901</startdate><enddate>20230901</enddate><creator>Xiang, Xuejiao</creator><creator>Chen, Jing</creator><creator>Jiang, Tao</creator><creator>Yan, Chengqi</creator><creator>Kang, Yu</creator><creator>Zhang, Maojie</creator><creator>Xiang, Kaituo</creator><creator>Guo, Jiahe</creator><creator>Jiang, Guoyong</creator><creator>Wang, Cheng</creator><creator>XiangXu</creator><creator>Yang, Xiaofan</creator><creator>Chen, Zhenbing</creator><general>Springer US</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>5PM</scope><orcidid>https://orcid.org/0000-0003-2828-866X</orcidid></search><sort><creationdate>20230901</creationdate><title>Milk-derived exosomes carrying siRNA-KEAP1 promote diabetic wound healing by improving oxidative stress</title><author>Xiang, Xuejiao ; Chen, Jing ; Jiang, Tao ; Yan, Chengqi ; Kang, Yu ; Zhang, Maojie ; Xiang, Kaituo ; Guo, Jiahe ; Jiang, Guoyong ; Wang, Cheng ; XiangXu ; Yang, Xiaofan ; Chen, Zhenbing</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c446t-9dca53a567cd64df9c2c334c8aee083a6f762f683119fee39d1ea1ed0afe99843</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Animals</topic><topic>Antioxidants - pharmacology</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Diabetes Mellitus, Experimental - drug therapy</topic><topic>Exosomes - metabolism</topic><topic>Human Umbilical Vein Endothelial Cells - metabolism</topic><topic>Humans</topic><topic>Kelch-Like ECH-Associated Protein 1 - metabolism</topic><topic>Magnesium Oxide - metabolism</topic><topic>Magnesium Oxide - pharmacology</topic><topic>Magnesium Oxide - therapeutic use</topic><topic>Mice</topic><topic>Milk - metabolism</topic><topic>NF-E2-Related Factor 2 - genetics</topic><topic>NF-E2-Related Factor 2 - metabolism</topic><topic>NF-E2-Related Factor 2 - pharmacology</topic><topic>Original</topic><topic>Original Article</topic><topic>Oxidative Stress</topic><topic>Pharmaceutical Sciences/Technology</topic><topic>Pyruvaldehyde - metabolism</topic><topic>Pyruvaldehyde - pharmacology</topic><topic>Pyruvaldehyde - therapeutic use</topic><topic>RNA, Small Interfering - pharmacology</topic><topic>Wound Healing</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Xiang, Xuejiao</creatorcontrib><creatorcontrib>Chen, Jing</creatorcontrib><creatorcontrib>Jiang, Tao</creatorcontrib><creatorcontrib>Yan, Chengqi</creatorcontrib><creatorcontrib>Kang, Yu</creatorcontrib><creatorcontrib>Zhang, Maojie</creatorcontrib><creatorcontrib>Xiang, Kaituo</creatorcontrib><creatorcontrib>Guo, Jiahe</creatorcontrib><creatorcontrib>Jiang, Guoyong</creatorcontrib><creatorcontrib>Wang, Cheng</creatorcontrib><creatorcontrib>XiangXu</creatorcontrib><creatorcontrib>Yang, Xiaofan</creatorcontrib><creatorcontrib>Chen, Zhenbing</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Drug delivery and translational research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Xiang, Xuejiao</au><au>Chen, Jing</au><au>Jiang, Tao</au><au>Yan, Chengqi</au><au>Kang, Yu</au><au>Zhang, Maojie</au><au>Xiang, Kaituo</au><au>Guo, Jiahe</au><au>Jiang, Guoyong</au><au>Wang, Cheng</au><au>XiangXu</au><au>Yang, Xiaofan</au><au>Chen, Zhenbing</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Milk-derived exosomes carrying siRNA-KEAP1 promote diabetic wound healing by improving oxidative stress</atitle><jtitle>Drug delivery and translational research</jtitle><stitle>Drug Deliv. and Transl. Res</stitle><addtitle>Drug Deliv Transl Res</addtitle><date>2023-09-01</date><risdate>2023</risdate><volume>13</volume><issue>9</issue><spage>2286</spage><epage>2296</epage><pages>2286-2296</pages><issn>2190-393X</issn><eissn>2190-3948</eissn><abstract>Diabetic wounds are a serious complication of diabetes mellitus (DM) that can lead to persistent infection, amputation, and even death. Prolonged oxidative stress has been widely recognized as a major instigator in the development of diabetic wounds; therefore, oxidative stress is considered a promising therapeutic target. In the present study, Keap1/Nrf2 signaling was confirmed to be activated in streptozotocin (STZ)-induced diabetic mice and methylglyoxal (MGO)-treated human umbilical vein endothelial cells (HUVECs). Knockdown of Keap1 by siRNA reversed the increase in Keap1 levels, promoted the nuclear translocation of Nrf2, and increased the expression of HO-1, an antioxidant protein. To explore therapeutic delivery strategies, milk-derived exosomes (mEXOs) were developed as a novel, efficient, and non-toxic siRNA carrier. SiRNA-Keap1 (siKeap1) was loaded into mEXOs by sonication, and the obtained mEXOs-siKeap1 were found to promote HUVEC proliferation and migration while relieving oxidative stress in MGO-treated HUVECs. Meanwhile, in a mouse model of diabetic wounds, injection of mEXOs-siKeap1 significantly accelerated diabetic wound healing with enhanced collagen formation and neovascularization. Taken together, these data support the development of Keap1 knockdown as a potential therapeutic strategy for diabetic wounds and demonstrated the feasibility of mEXOs as a scalable, biocompatible, and cost-effective siRNA delivery system.
Graphical Abstract
The therapeutic effect of siKeap1-loaded mEXOs on diabetic wound healing was assessed. First, we found that the expression of Keap1 was upregulated in the wounds of diabetic mice and in human umbilical vein endothelial cells (HUVECs) pretreated with methylglyoxal (MGO). Next, we extracted exosomes from raw milk by differential centrifugation and loaded siKeap1 into milk-derived exosomes by sonication. The in vitro application of the synthetic complex (mEXOs-siKeap1) was found to increase the nuclear localization of Nrf2 and the expression of the antioxidant protein HO-1, thus reversing oxidative stress. Furthermore, in vivo mEXOs-siKeap1 administration significantly accelerated the healing rate of diabetic wounds (Scheme 1).
Scheme 1
Schematic diagram.
A
Synthesis of mEXOs-siKeap1 complex.
B
Mechanism of mEXOs-siKeap1 in vitro.
C
The treatment effect of mEXOs-siKeap1 on an in vivo mouse model of diabetic wounds</abstract><cop>New York</cop><pub>Springer US</pub><pmid>36749479</pmid><doi>10.1007/s13346-023-01306-x</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0003-2828-866X</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 2190-393X |
| ispartof | Drug delivery and translational research, 2023-09, Vol.13 (9), p.2286-2296 |
| issn | 2190-393X 2190-3948 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_9904251 |
| source | MEDLINE; SpringerLink Journals - AutoHoldings |
| subjects | Animals Antioxidants - pharmacology Biomedical and Life Sciences Biomedicine Diabetes Mellitus, Experimental - drug therapy Exosomes - metabolism Human Umbilical Vein Endothelial Cells - metabolism Humans Kelch-Like ECH-Associated Protein 1 - metabolism Magnesium Oxide - metabolism Magnesium Oxide - pharmacology Magnesium Oxide - therapeutic use Mice Milk - metabolism NF-E2-Related Factor 2 - genetics NF-E2-Related Factor 2 - metabolism NF-E2-Related Factor 2 - pharmacology Original Original Article Oxidative Stress Pharmaceutical Sciences/Technology Pyruvaldehyde - metabolism Pyruvaldehyde - pharmacology Pyruvaldehyde - therapeutic use RNA, Small Interfering - pharmacology Wound Healing |
| title | Milk-derived exosomes carrying siRNA-KEAP1 promote diabetic wound healing by improving oxidative stress |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-13T18%3A44%3A41IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-pubmed_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Milk-derived%20exosomes%20carrying%20siRNA-KEAP1%20promote%20diabetic%20wound%20healing%20by%20improving%20oxidative%20stress&rft.jtitle=Drug%20delivery%20and%20translational%20research&rft.au=Xiang,%20Xuejiao&rft.date=2023-09-01&rft.volume=13&rft.issue=9&rft.spage=2286&rft.epage=2296&rft.pages=2286-2296&rft.issn=2190-393X&rft.eissn=2190-3948&rft_id=info:doi/10.1007/s13346-023-01306-x&rft_dat=%3Cpubmed_cross%3E36749479%3C/pubmed_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_id=info:pmid/36749479&rfr_iscdi=true |