Maresin-2 promotes mucosal repair and has therapeutic potential when encapsulated in thermostable nanoparticles
Resolution of inflammation and mucosal wound healing are crucial processes required to re-establish homeostasis following injury of mucosal tissues. Maresin-2 (MaR2), a lipid specialized pro-resolving mediator derived from omega-3 polyunsaturated fatty acid, has been reported to promote resolution of inflammation. However, a potential role for MaR2 in regulating mucosal repair remains undefined. Using lipidomic analyses, we demonstrate biosynthesis of MaR2 in healing intestinal mucosal wounds in vivo. Importantly, administration of exogenous MaR2 promoted mucosal repair following dextran sulfate sodium-induced colitis or biopsy-induced colonic mucosal injury. Functional analyses revealed that MaR2 promotes mucosal wound repair by driving intestinal epithelial migration through activation of focal cell-matrix adhesion signaling in primary human intestinal epithelial cells. Because of its labile nature, MaR2 is easily degradable and requires ultracold storage to maintain functionality. Thus, we created thermostable polylactic acid MaR2 nanoparticles that retain biological activity following extended storage at 4 °C or above. Taken together, these results establish MaR2 as a potent pro-repair lipid mediator with broad therapeutic potential for use in promoting mucosal repair in inflammatory diseases.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2023 |
|---|---|
| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:120 |
|---|---|
| Enthalten in: |
Proceedings of the National Academy of Sciences of the United States of America - 120(2023), 4 vom: 24. Jan., Seite e2218162120 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Miranda, Jael [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
9042-14-2 |
|---|
| Anmerkungen: |
Date Completed 24.01.2023 Date Revised 16.11.2023 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1073/pnas.2218162120 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM351798269 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM351798269 | ||
| 003 | DE-627 | ||
| 005 | 20231226052232.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2023 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1073/pnas.2218162120 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1172.xml |
| 035 | |a (DE-627)NLM351798269 | ||
| 035 | |a (NLM)36669099 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Miranda, Jael |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Maresin-2 promotes mucosal repair and has therapeutic potential when encapsulated in thermostable nanoparticles |
| 264 | 1 | |c 2023 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 24.01.2023 | ||
| 500 | |a Date Revised 16.11.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Resolution of inflammation and mucosal wound healing are crucial processes required to re-establish homeostasis following injury of mucosal tissues. Maresin-2 (MaR2), a lipid specialized pro-resolving mediator derived from omega-3 polyunsaturated fatty acid, has been reported to promote resolution of inflammation. However, a potential role for MaR2 in regulating mucosal repair remains undefined. Using lipidomic analyses, we demonstrate biosynthesis of MaR2 in healing intestinal mucosal wounds in vivo. Importantly, administration of exogenous MaR2 promoted mucosal repair following dextran sulfate sodium-induced colitis or biopsy-induced colonic mucosal injury. Functional analyses revealed that MaR2 promotes mucosal wound repair by driving intestinal epithelial migration through activation of focal cell-matrix adhesion signaling in primary human intestinal epithelial cells. Because of its labile nature, MaR2 is easily degradable and requires ultracold storage to maintain functionality. Thus, we created thermostable polylactic acid MaR2 nanoparticles that retain biological activity following extended storage at 4 °C or above. Taken together, these results establish MaR2 as a potent pro-repair lipid mediator with broad therapeutic potential for use in promoting mucosal repair in inflammatory diseases | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a epithelia | |
| 650 | 4 | |a mucosal repair | |
| 650 | 4 | |a nanoparticles | |
| 650 | 4 | |a resolution of inflammation | |
| 650 | 4 | |a specialized pro-resolving mediators | |
| 650 | 7 | |a Dextran Sulfate |2 NLM | |
| 650 | 7 | |a 9042-14-2 |2 NLM | |
| 700 | 1 | |a Brazil, Jennifer C |e verfasserin |4 aut | |
| 700 | 1 | |a Morris, Aaron H |e verfasserin |4 aut | |
| 700 | 1 | |a Parkos, Charles A |e verfasserin |4 aut | |
| 700 | 1 | |a Quiros, Miguel |e verfasserin |4 aut | |
| 700 | 1 | |a Nusrat, Asma |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Proceedings of the National Academy of Sciences of the United States of America |d 1915 |g 120(2023), 4 vom: 24. Jan., Seite e2218162120 |w (DE-627)NLM000008982 |x 1091-6490 |7 nnns |
| 773 | 1 | 8 | |g volume:120 |g year:2023 |g number:4 |g day:24 |g month:01 |g pages:e2218162120 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1073/pnas.2218162120 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 120 |j 2023 |e 4 |b 24 |c 01 |h e2218162120 | ||