55270 The Histone Methyltransferase SETDB2 Regulates Inflammation in Normal and Diabetic Wound Repair
ABSTRACT IMPACT: Our data reveal a histone modifying enzyme involved in regulating inflammation that may be a novel target for treating non-healing diabetic wounds. OBJECTIVES/GOALS: We investigate molecular mechanisms that regulate the inflammatory phenotype of macrophages in normal and diabetic wo...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Cambridge University Press
2021-03-01
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| Series: | Journal of Clinical and Translational Science |
| Online Access: | https://www.cambridge.org/core/product/identifier/S2059866121004416/type/journal_article |
| _version_ | 1811155271693631488 |
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| author | Aaron denDekker Frank Davis Andrew Kimball Matthew Schaller Amrita Joshi Ronald Allen Katherine Gallagher |
| author_facet | Aaron denDekker Frank Davis Andrew Kimball Matthew Schaller Amrita Joshi Ronald Allen Katherine Gallagher |
| author_sort | Aaron denDekker |
| collection | DOAJ |
| description | ABSTRACT IMPACT: Our data reveal a histone modifying enzyme involved in regulating inflammation that may be a novel target for treating non-healing diabetic wounds. OBJECTIVES/GOALS: We investigate molecular mechanisms that regulate the inflammatory phenotype of macrophages in normal and diabetic wound healing. Our goal is to identify novel pathways that may be used to better treat diabetic patients with non-healing wounds. METHODS/STUDY POPULATION: We utilize normal and transgenic murine models on standard chow or high-diet to identify chromatin modifying enzymes involved in regulating macrophage function during wound healing. We validate our murine studies with human blood monocytes or wound macrophages from diabetic patients undergoing limb amputation surgery. RESULTS/ANTICIPATED RESULTS: We have identified the histone methyltransferase SETDB2 as a regulator inflammation in normal and diabetic wound macrophages. We found that SETDB2 was dependent on IFNβ singaling and that both IFNβ and Setdb2 expression were impaired in diabetic wound macrophages. Further, we show that SETDB2 regulates inflammatory response and immune cell trafficking pathways. We also show that SETDB2 genomic localization is dependent on *NFκΒ deposition of the promoter. DISCUSSION/SIGNIFICANCE OF FINDINGS: Our results indicate that SETDB2 is a regulator of macrophage plasticity and that SETDB2 expression is impaired in diabetic wound macrophages leading to hyper-inflammatory response and delayed wound healing. These data provide a novel potential therapeutic pathway for treating non-healing diabetic wounds. |
| first_indexed | 2024-04-10T04:31:28Z |
| format | Article |
| id | doaj.art-24cadedcddf541798ad547763b2e04ea |
| institution | Directory Open Access Journal |
| issn | 2059-8661 |
| language | English |
| last_indexed | 2024-04-10T04:31:28Z |
| publishDate | 2021-03-01 |
| publisher | Cambridge University Press |
| record_format | Article |
| series | Journal of Clinical and Translational Science |
| spelling | doaj.art-24cadedcddf541798ad547763b2e04ea2023-03-10T07:52:04ZengCambridge University PressJournal of Clinical and Translational Science2059-86612021-03-015151510.1017/cts.2021.44155270 The Histone Methyltransferase SETDB2 Regulates Inflammation in Normal and Diabetic Wound RepairAaron denDekker0Frank Davis1Andrew Kimball2Matthew Schaller3Amrita Joshi4Ronald Allen5Katherine Gallagher6University of MichiganUniversity of MichiganUniversity of Alabama-BirminghamUniversity of FloridaUniversity of MichiganUniversity of MichiganUniversity of MichiganABSTRACT IMPACT: Our data reveal a histone modifying enzyme involved in regulating inflammation that may be a novel target for treating non-healing diabetic wounds. OBJECTIVES/GOALS: We investigate molecular mechanisms that regulate the inflammatory phenotype of macrophages in normal and diabetic wound healing. Our goal is to identify novel pathways that may be used to better treat diabetic patients with non-healing wounds. METHODS/STUDY POPULATION: We utilize normal and transgenic murine models on standard chow or high-diet to identify chromatin modifying enzymes involved in regulating macrophage function during wound healing. We validate our murine studies with human blood monocytes or wound macrophages from diabetic patients undergoing limb amputation surgery. RESULTS/ANTICIPATED RESULTS: We have identified the histone methyltransferase SETDB2 as a regulator inflammation in normal and diabetic wound macrophages. We found that SETDB2 was dependent on IFNβ singaling and that both IFNβ and Setdb2 expression were impaired in diabetic wound macrophages. Further, we show that SETDB2 regulates inflammatory response and immune cell trafficking pathways. We also show that SETDB2 genomic localization is dependent on *NFκΒ deposition of the promoter. DISCUSSION/SIGNIFICANCE OF FINDINGS: Our results indicate that SETDB2 is a regulator of macrophage plasticity and that SETDB2 expression is impaired in diabetic wound macrophages leading to hyper-inflammatory response and delayed wound healing. These data provide a novel potential therapeutic pathway for treating non-healing diabetic wounds.https://www.cambridge.org/core/product/identifier/S2059866121004416/type/journal_article |
| spellingShingle | Aaron denDekker Frank Davis Andrew Kimball Matthew Schaller Amrita Joshi Ronald Allen Katherine Gallagher 55270 The Histone Methyltransferase SETDB2 Regulates Inflammation in Normal and Diabetic Wound Repair Journal of Clinical and Translational Science |
| title | 55270 The Histone Methyltransferase SETDB2 Regulates Inflammation in Normal and Diabetic Wound Repair |
| title_full | 55270 The Histone Methyltransferase SETDB2 Regulates Inflammation in Normal and Diabetic Wound Repair |
| title_fullStr | 55270 The Histone Methyltransferase SETDB2 Regulates Inflammation in Normal and Diabetic Wound Repair |
| title_full_unstemmed | 55270 The Histone Methyltransferase SETDB2 Regulates Inflammation in Normal and Diabetic Wound Repair |
| title_short | 55270 The Histone Methyltransferase SETDB2 Regulates Inflammation in Normal and Diabetic Wound Repair |
| title_sort | 55270 the histone methyltransferase setdb2 regulates inflammation in normal and diabetic wound repair |
| url | https://www.cambridge.org/core/product/identifier/S2059866121004416/type/journal_article |
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