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QS1: Creeping Fat Adipocytes Drive Intestinal Fibrosis Through Adipocyte-to-fibroblast Conversion in a Novel Model of Inflammatory Bowel Disease
PURPOSE: Crohn’s disease (CD) is a subtype of inflammatory bowel disease (IBD) characterized by patchy, transmural inflammation throughout the digestive tract and creeping fat formation. Thirty percent of CD patients develop strictures, eighty percent of which will require surgery. Creeping fat is a...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Lippincott Williams & Wilkins
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8312823/ http://dx.doi.org/10.1097/01.GOX.0000769952.79242.cc |
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author | Bauer-Rowe, Khristian E. Hyunh, Jeong Foster, Deshka S. Griffin, Michelle Mascharak, Shamik desJardins-Park, Heather Norton, Jeffrey A. Longaker, Michael T. |
author_facet | Bauer-Rowe, Khristian E. Hyunh, Jeong Foster, Deshka S. Griffin, Michelle Mascharak, Shamik desJardins-Park, Heather Norton, Jeffrey A. Longaker, Michael T. |
author_sort | Bauer-Rowe, Khristian E. |
collection | PubMed |
description | PURPOSE: Crohn’s disease (CD) is a subtype of inflammatory bowel disease (IBD) characterized by patchy, transmural inflammation throughout the digestive tract and creeping fat formation. Thirty percent of CD patients develop strictures, eighty percent of which will require surgery. Creeping fat is associated with stricture formation, but its role in intestinal fibrosis remains unclear. Here, we present a novel surgical model of intestinal fibrosis and show by lineage tracing that creeping fat adipocytes convert to fibroblasts that contribute to fibrosis. METHODS: We developed a novel surgical model of IBD that avoids the chronic use of caustic agents by creating a longitudinal, anti-mesenteric colotomy in the mouse transverse colon that is closed transversally. We performed Masson’s trichrome staining to assess collagen deposition. Finally, we performed lineage tracing of mature adipocytes in Adiponectin-Cre; mTmG mice and characterized adipocyte-derived cells by immunostaining. RESULTS: Our surgical model mimics key features of human strictures, including the formation of creeping fat around the injury site, increased bowel wall thickness, collagen deposition, and transmural adipocyte infiltration by post-operative day (POD) 7. Immunostaining for adipocyte and fibroblast markers confirmed the presence of transmural adipocytes adjacent to fibroblasts. Lineage tracing of mature adipocytes in Adiponectin-Cre; mTmG mice revealed adipocyte-derived cells that infiltrate the wound site that lose expression of adipocyte lineage markers, gain expression of fibroblast markers, produce collagen, and respond to TGF-β signaling. CONCLUSIONS: Our novel surgical colotomy model represents a viable approach to study intestinal fibrosis and creeping fat without the long-term use of caustic agents. Lineage tracing of mature creeping fat adipocytes demonstrates that adipocytes convert to fibroblasts that infiltrate the injury site and participate in fibrotic responses. Taken together, these findings suggest that creeping fat contributes to intestinal fibrosis in part through the local conversion of adipocytes to fibroblasts. |
format | Online Article Text |
id | pubmed-8312823 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Lippincott Williams & Wilkins |
record_format | MEDLINE/PubMed |
spelling | pubmed-83128232021-07-27 QS1: Creeping Fat Adipocytes Drive Intestinal Fibrosis Through Adipocyte-to-fibroblast Conversion in a Novel Model of Inflammatory Bowel Disease Bauer-Rowe, Khristian E. Hyunh, Jeong Foster, Deshka S. Griffin, Michelle Mascharak, Shamik desJardins-Park, Heather Norton, Jeffrey A. Longaker, Michael T. Plast Reconstr Surg Glob Open PSRC 2021 Abstract Supplement PURPOSE: Crohn’s disease (CD) is a subtype of inflammatory bowel disease (IBD) characterized by patchy, transmural inflammation throughout the digestive tract and creeping fat formation. Thirty percent of CD patients develop strictures, eighty percent of which will require surgery. Creeping fat is associated with stricture formation, but its role in intestinal fibrosis remains unclear. Here, we present a novel surgical model of intestinal fibrosis and show by lineage tracing that creeping fat adipocytes convert to fibroblasts that contribute to fibrosis. METHODS: We developed a novel surgical model of IBD that avoids the chronic use of caustic agents by creating a longitudinal, anti-mesenteric colotomy in the mouse transverse colon that is closed transversally. We performed Masson’s trichrome staining to assess collagen deposition. Finally, we performed lineage tracing of mature adipocytes in Adiponectin-Cre; mTmG mice and characterized adipocyte-derived cells by immunostaining. RESULTS: Our surgical model mimics key features of human strictures, including the formation of creeping fat around the injury site, increased bowel wall thickness, collagen deposition, and transmural adipocyte infiltration by post-operative day (POD) 7. Immunostaining for adipocyte and fibroblast markers confirmed the presence of transmural adipocytes adjacent to fibroblasts. Lineage tracing of mature adipocytes in Adiponectin-Cre; mTmG mice revealed adipocyte-derived cells that infiltrate the wound site that lose expression of adipocyte lineage markers, gain expression of fibroblast markers, produce collagen, and respond to TGF-β signaling. CONCLUSIONS: Our novel surgical colotomy model represents a viable approach to study intestinal fibrosis and creeping fat without the long-term use of caustic agents. Lineage tracing of mature creeping fat adipocytes demonstrates that adipocytes convert to fibroblasts that infiltrate the injury site and participate in fibrotic responses. Taken together, these findings suggest that creeping fat contributes to intestinal fibrosis in part through the local conversion of adipocytes to fibroblasts. Lippincott Williams & Wilkins 2021-07-26 /pmc/articles/PMC8312823/ http://dx.doi.org/10.1097/01.GOX.0000769952.79242.cc Text en Copyright © 2021 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons. All rights reserved. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) , where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. |
spellingShingle | PSRC 2021 Abstract Supplement Bauer-Rowe, Khristian E. Hyunh, Jeong Foster, Deshka S. Griffin, Michelle Mascharak, Shamik desJardins-Park, Heather Norton, Jeffrey A. Longaker, Michael T. QS1: Creeping Fat Adipocytes Drive Intestinal Fibrosis Through Adipocyte-to-fibroblast Conversion in a Novel Model of Inflammatory Bowel Disease |
title | QS1: Creeping Fat Adipocytes Drive Intestinal Fibrosis Through Adipocyte-to-fibroblast Conversion in a Novel Model of Inflammatory Bowel Disease |
title_full | QS1: Creeping Fat Adipocytes Drive Intestinal Fibrosis Through Adipocyte-to-fibroblast Conversion in a Novel Model of Inflammatory Bowel Disease |
title_fullStr | QS1: Creeping Fat Adipocytes Drive Intestinal Fibrosis Through Adipocyte-to-fibroblast Conversion in a Novel Model of Inflammatory Bowel Disease |
title_full_unstemmed | QS1: Creeping Fat Adipocytes Drive Intestinal Fibrosis Through Adipocyte-to-fibroblast Conversion in a Novel Model of Inflammatory Bowel Disease |
title_short | QS1: Creeping Fat Adipocytes Drive Intestinal Fibrosis Through Adipocyte-to-fibroblast Conversion in a Novel Model of Inflammatory Bowel Disease |
title_sort | qs1: creeping fat adipocytes drive intestinal fibrosis through adipocyte-to-fibroblast conversion in a novel model of inflammatory bowel disease |
topic | PSRC 2021 Abstract Supplement |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8312823/ http://dx.doi.org/10.1097/01.GOX.0000769952.79242.cc |
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