Inhibition of Soluble Stem Cell Factor Promotes Intestinal Mucosal Repair
© The Author(s) 2023. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For permissions, please e-mail: journals.permissionsoup.com..
BACKGROUND: Incidences of inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, are escalating worldwide and can be considered a global public health problem. Given that the gold standard approach to IBD therapeutics focuses on reducing the severity of symptoms, there is an urgent unmet need to develop alternative therapies that halt not only inflammatory processes but also promote mucosal repair. Previous studies have identified increased stem cell factor (SCF) expression in inflamed intestinal mucosal tissues. However, the role that SCF plays in mediating intestinal inflammation and repair has not been explored.
METHODS: Changes in the expression of SCF were evaluated in the colonic tissue of healthy mice and during dextran sodium sulfate (DSS)-induced colitis. Furthermore, mucosal wound healing and colitis severity were analyzed in mice subjected to either mechanical biopsy or DSS treatment, respectively, following intestinal epithelial cell-specific deletion of SCF or anti-SCF antibody administration.
RESULTS: We report robust expression of SCF by intestinal epithelial cells during intestinal homeostasis with a switch to immune cell-produced SCF during colitis. Data from mice with intestinal epithelial cell-specific deletion of SCF highlight the importance of immune cell-produced SCF in driving the pathogenesis of colitis. Importantly, antibody-mediated neutralization of total SCF or the specific SCF248 isoform decreased immune cell infiltration and enhanced mucosal wound repair following biopsy-induced colonic injury or DSS-induced colitis.
CONCLUSIONS: These data demonstrate that SCF functions as a pro-inflammatory mediator in mucosal tissues and that specific neutralization of SCF248 could be a viable therapeutic option to reduce intestinal inflammation and promote mucosal wound repair in individuals with IBD.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:29 |
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| Enthalten in: |
Inflammatory bowel diseases - 29(2023), 7 vom: 05. Juli, Seite 1133-1144 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Garcia-Hernandez, Vicky [VerfasserIn] |
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| Links: |
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| Themen: |
9042-14-2 |
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| Anmerkungen: |
Date Completed 07.07.2023 Date Revised 24.01.2024 published: Print Citation Status MEDLINE |
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| doi: |
10.1093/ibd/izad003 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM351991689 |
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| 245 | 1 | 0 | |a Inhibition of Soluble Stem Cell Factor Promotes Intestinal Mucosal Repair |
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| 520 | |a © The Author(s) 2023. Published by Oxford University Press on behalf of Crohn’s & Colitis Foundation. All rights reserved. For permissions, please e-mail: journals.permissionsoup.com. | ||
| 520 | |a BACKGROUND: Incidences of inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, are escalating worldwide and can be considered a global public health problem. Given that the gold standard approach to IBD therapeutics focuses on reducing the severity of symptoms, there is an urgent unmet need to develop alternative therapies that halt not only inflammatory processes but also promote mucosal repair. Previous studies have identified increased stem cell factor (SCF) expression in inflamed intestinal mucosal tissues. However, the role that SCF plays in mediating intestinal inflammation and repair has not been explored | ||
| 520 | |a METHODS: Changes in the expression of SCF were evaluated in the colonic tissue of healthy mice and during dextran sodium sulfate (DSS)-induced colitis. Furthermore, mucosal wound healing and colitis severity were analyzed in mice subjected to either mechanical biopsy or DSS treatment, respectively, following intestinal epithelial cell-specific deletion of SCF or anti-SCF antibody administration | ||
| 520 | |a RESULTS: We report robust expression of SCF by intestinal epithelial cells during intestinal homeostasis with a switch to immune cell-produced SCF during colitis. Data from mice with intestinal epithelial cell-specific deletion of SCF highlight the importance of immune cell-produced SCF in driving the pathogenesis of colitis. Importantly, antibody-mediated neutralization of total SCF or the specific SCF248 isoform decreased immune cell infiltration and enhanced mucosal wound repair following biopsy-induced colonic injury or DSS-induced colitis | ||
| 520 | |a CONCLUSIONS: These data demonstrate that SCF functions as a pro-inflammatory mediator in mucosal tissues and that specific neutralization of SCF248 could be a viable therapeutic option to reduce intestinal inflammation and promote mucosal wound repair in individuals with IBD | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a IBD | |
| 650 | 4 | |a epithelia | |
| 650 | 4 | |a intestine | |
| 650 | 4 | |a mucosal repair | |
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| 700 | 1 | |a Raya-Sandino, Arturo |e verfasserin |4 aut | |
| 700 | 1 | |a Azcutia, Veronica |e verfasserin |4 aut | |
| 700 | 1 | |a Miranda, Jael |e verfasserin |4 aut | |
| 700 | 1 | |a Kelm, Matthias |e verfasserin |4 aut | |
| 700 | 1 | |a Flemming, Sven |e verfasserin |4 aut | |
| 700 | 1 | |a Birkl, Dorothee |e verfasserin |4 aut | |
| 700 | 1 | |a Quiros, Miguel |e verfasserin |4 aut | |
| 700 | 1 | |a Brazil, Jennifer C |e verfasserin |4 aut | |
| 700 | 1 | |a Parkos, Charles A |e verfasserin |4 aut | |
| 700 | 1 | |a Nusrat, Asma |e verfasserin |4 aut | |
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