miR-511 Deficiency Protects Mice from Experimental Colitis by Reducing TLR3 and TLR4 Responses via WD Repeat and FYVE-Domain-Containing Protein 1
Antimicrobial responses play an important role in maintaining intestinal heath. Recently we reported that miR-511 may regulate TLR4 responses leading to enhanced intestinal inflammation. However, the exact mechanism remained unclear. In this study we investigated the effect of miR-511 deficiency on...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-12-01
|
| Series: | Cells |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4409/11/1/58 |
| _version_ | 1797499391863422976 |
|---|---|
| author | Shafaque Rahman Jolien Vandewalle Patricia H. P. van Hamersveld Caroline Verseijden Olaf Welting Aldo Jongejan Pierina Casanova Sybren L. Meijer Claude Libert Theodorus B. M. Hakvoort Wouter J. de Jonge Sigrid E. M. Heinsbroek |
| author_facet | Shafaque Rahman Jolien Vandewalle Patricia H. P. van Hamersveld Caroline Verseijden Olaf Welting Aldo Jongejan Pierina Casanova Sybren L. Meijer Claude Libert Theodorus B. M. Hakvoort Wouter J. de Jonge Sigrid E. M. Heinsbroek |
| author_sort | Shafaque Rahman |
| collection | DOAJ |
| description | Antimicrobial responses play an important role in maintaining intestinal heath. Recently we reported that miR-511 may regulate TLR4 responses leading to enhanced intestinal inflammation. However, the exact mechanism remained unclear. In this study we investigated the effect of miR-511 deficiency on anti-microbial responses and DSS-induced intestinal inflammation. miR-511-deficient mice were protected from DSS-induced colitis as shown by significantly lower disease activity index, weight loss and histology scores in the miR-511-deficient group. Furthermore, reduced inflammatory cytokine responses were observed in colons of miR-511 deficient mice. In vitro studies with bone marrow-derived M2 macrophages showed reduced TLR3 and TLR4 responses in miR-511-deficient macrophages compared to WT macrophages. Subsequent RNA sequencing revealed Wdfy1 as the potential miR-511 target. WDFY1 deficiency is related to impaired TLR3/TLR4 immune responses and the expression was downregulated in miR-511-deficient macrophages and colons. Together, this study shows that miR-511 is involved in the regulation of intestinal inflammation through downstream regulation of TLR3 and TLR4 responses via Wdfy1. |
| first_indexed | 2024-03-10T03:46:40Z |
| format | Article |
| id | doaj.art-b85d403e380c4f349943048a274f5266 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T03:46:40Z |
| publishDate | 2021-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-b85d403e380c4f349943048a274f52662023-11-23T11:19:33ZengMDPI AGCells2073-44092021-12-011115810.3390/cells11010058miR-511 Deficiency Protects Mice from Experimental Colitis by Reducing TLR3 and TLR4 Responses via WD Repeat and FYVE-Domain-Containing Protein 1Shafaque Rahman0Jolien Vandewalle1Patricia H. P. van Hamersveld2Caroline Verseijden3Olaf Welting4Aldo Jongejan5Pierina Casanova6Sybren L. Meijer7Claude Libert8Theodorus B. M. Hakvoort9Wouter J. de Jonge10Sigrid E. M. Heinsbroek11Tytgat Institute for Liver and Intestinal Research, Amsterdam Gastroenterology Endocrinology and Metabolism, Amsterdam University Medical Centers, Location AMC, University of Amsterdam, 1105 BK Amsterdam, The NetherlandsDepartment of Biomedical Molecular Biology, Ghent University, 9052 Ghent, BelgiumTytgat Institute for Liver and Intestinal Research, Amsterdam Gastroenterology Endocrinology and Metabolism, Amsterdam University Medical Centers, Location AMC, University of Amsterdam, 1105 BK Amsterdam, The NetherlandsTytgat Institute for Liver and Intestinal Research, Amsterdam Gastroenterology Endocrinology and Metabolism, Amsterdam University Medical Centers, Location AMC, University of Amsterdam, 1105 BK Amsterdam, The NetherlandsTytgat Institute for Liver and Intestinal Research, Amsterdam Gastroenterology Endocrinology and Metabolism, Amsterdam University Medical Centers, Location AMC, University of Amsterdam, 1105 BK Amsterdam, The NetherlandsBioinformatics Laboratory, Department of Epidemiology and Data Science, Amsterdam University Medical Centers, Location AMC, University of Amsterdam, 1105 AZ Amsterdam, The NetherlandsTytgat Institute for Liver and Intestinal Research, Amsterdam Gastroenterology Endocrinology and Metabolism, Amsterdam University Medical Centers, Location AMC, University of Amsterdam, 1105 BK Amsterdam, The NetherlandsDepartment of Pathology, Amsterdam University Medical Centers, Location AMC, University of Amsterdam, 1105 AZ Amsterdam, The NetherlandsDepartment of Biomedical Molecular Biology, Ghent University, 9052 Ghent, BelgiumTytgat Institute for Liver and Intestinal Research, Amsterdam Gastroenterology Endocrinology and Metabolism, Amsterdam University Medical Centers, Location AMC, University of Amsterdam, 1105 BK Amsterdam, The NetherlandsTytgat Institute for Liver and Intestinal Research, Amsterdam Gastroenterology Endocrinology and Metabolism, Amsterdam University Medical Centers, Location AMC, University of Amsterdam, 1105 BK Amsterdam, The NetherlandsTytgat Institute for Liver and Intestinal Research, Amsterdam Gastroenterology Endocrinology and Metabolism, Amsterdam University Medical Centers, Location AMC, University of Amsterdam, 1105 BK Amsterdam, The NetherlandsAntimicrobial responses play an important role in maintaining intestinal heath. Recently we reported that miR-511 may regulate TLR4 responses leading to enhanced intestinal inflammation. However, the exact mechanism remained unclear. In this study we investigated the effect of miR-511 deficiency on anti-microbial responses and DSS-induced intestinal inflammation. miR-511-deficient mice were protected from DSS-induced colitis as shown by significantly lower disease activity index, weight loss and histology scores in the miR-511-deficient group. Furthermore, reduced inflammatory cytokine responses were observed in colons of miR-511 deficient mice. In vitro studies with bone marrow-derived M2 macrophages showed reduced TLR3 and TLR4 responses in miR-511-deficient macrophages compared to WT macrophages. Subsequent RNA sequencing revealed Wdfy1 as the potential miR-511 target. WDFY1 deficiency is related to impaired TLR3/TLR4 immune responses and the expression was downregulated in miR-511-deficient macrophages and colons. Together, this study shows that miR-511 is involved in the regulation of intestinal inflammation through downstream regulation of TLR3 and TLR4 responses via Wdfy1.https://www.mdpi.com/2073-4409/11/1/58miR-511intestinal inflammationmousewdfy1TLRs |
| spellingShingle | Shafaque Rahman Jolien Vandewalle Patricia H. P. van Hamersveld Caroline Verseijden Olaf Welting Aldo Jongejan Pierina Casanova Sybren L. Meijer Claude Libert Theodorus B. M. Hakvoort Wouter J. de Jonge Sigrid E. M. Heinsbroek miR-511 Deficiency Protects Mice from Experimental Colitis by Reducing TLR3 and TLR4 Responses via WD Repeat and FYVE-Domain-Containing Protein 1 Cells miR-511 intestinal inflammation mouse wdfy1 TLRs |
| title | miR-511 Deficiency Protects Mice from Experimental Colitis by Reducing TLR3 and TLR4 Responses via WD Repeat and FYVE-Domain-Containing Protein 1 |
| title_full | miR-511 Deficiency Protects Mice from Experimental Colitis by Reducing TLR3 and TLR4 Responses via WD Repeat and FYVE-Domain-Containing Protein 1 |
| title_fullStr | miR-511 Deficiency Protects Mice from Experimental Colitis by Reducing TLR3 and TLR4 Responses via WD Repeat and FYVE-Domain-Containing Protein 1 |
| title_full_unstemmed | miR-511 Deficiency Protects Mice from Experimental Colitis by Reducing TLR3 and TLR4 Responses via WD Repeat and FYVE-Domain-Containing Protein 1 |
| title_short | miR-511 Deficiency Protects Mice from Experimental Colitis by Reducing TLR3 and TLR4 Responses via WD Repeat and FYVE-Domain-Containing Protein 1 |
| title_sort | mir 511 deficiency protects mice from experimental colitis by reducing tlr3 and tlr4 responses via wd repeat and fyve domain containing protein 1 |
| topic | miR-511 intestinal inflammation mouse wdfy1 TLRs |
| url | https://www.mdpi.com/2073-4409/11/1/58 |
| work_keys_str_mv | AT shafaquerahman mir511deficiencyprotectsmicefromexperimentalcolitisbyreducingtlr3andtlr4responsesviawdrepeatandfyvedomaincontainingprotein1 AT jolienvandewalle mir511deficiencyprotectsmicefromexperimentalcolitisbyreducingtlr3andtlr4responsesviawdrepeatandfyvedomaincontainingprotein1 AT patriciahpvanhamersveld mir511deficiencyprotectsmicefromexperimentalcolitisbyreducingtlr3andtlr4responsesviawdrepeatandfyvedomaincontainingprotein1 AT carolineverseijden mir511deficiencyprotectsmicefromexperimentalcolitisbyreducingtlr3andtlr4responsesviawdrepeatandfyvedomaincontainingprotein1 AT olafwelting mir511deficiencyprotectsmicefromexperimentalcolitisbyreducingtlr3andtlr4responsesviawdrepeatandfyvedomaincontainingprotein1 AT aldojongejan mir511deficiencyprotectsmicefromexperimentalcolitisbyreducingtlr3andtlr4responsesviawdrepeatandfyvedomaincontainingprotein1 AT pierinacasanova mir511deficiencyprotectsmicefromexperimentalcolitisbyreducingtlr3andtlr4responsesviawdrepeatandfyvedomaincontainingprotein1 AT sybrenlmeijer mir511deficiencyprotectsmicefromexperimentalcolitisbyreducingtlr3andtlr4responsesviawdrepeatandfyvedomaincontainingprotein1 AT claudelibert mir511deficiencyprotectsmicefromexperimentalcolitisbyreducingtlr3andtlr4responsesviawdrepeatandfyvedomaincontainingprotein1 AT theodorusbmhakvoort mir511deficiencyprotectsmicefromexperimentalcolitisbyreducingtlr3andtlr4responsesviawdrepeatandfyvedomaincontainingprotein1 AT wouterjdejonge mir511deficiencyprotectsmicefromexperimentalcolitisbyreducingtlr3andtlr4responsesviawdrepeatandfyvedomaincontainingprotein1 AT sigridemheinsbroek mir511deficiencyprotectsmicefromexperimentalcolitisbyreducingtlr3andtlr4responsesviawdrepeatandfyvedomaincontainingprotein1 |