@article{9f4cf7359bdb4a459bf9c55e0305e991,
title = "Adaptation of extracellular matrix to massive small bowel resection in mice",
abstract = "Background: Extracellular matrix (ECM) affects cell behavior, and vice versa. How ECM changes after small bowel resection (SBR) to support adaptive cellular processes has not been described. Here we characterize changes in ECM following SBR and integrate this with concomitant transcriptional perturbations. Methods: A 50% proximal SBR or sham surgery was performed on mice. On postoperative day 7, ileal tissue was sequentially depleted of protein components to generate an ECM-enriched fraction. ECM was analyzed for protein composition using mass spectrometry with subsequent Ingenuity Pathway Analysis (IPA) to identify predicted pathways and upstream regulators. qPCR and RNA-sequencing (RNA-Seq) were performed to corroborate these predicted pathways. Results: 3034 proteins were differentially regulated between sham and SBR, of which 95 were significant (P < 0.05). IPA analysis predicted PPARα agonism to be an upstream regulator of the observed proteomic changes (P < 0.001). qPCR and RNA-Seq with KEGG analysis confirmed significant engagement of the PPAR pathway (P < 0.05). Conclusion: Transcriptional signatures of adapting bowel predict subsequent ECM changes after SBR. How ECM communicates with surrounding cells to drive adaptation and vice versa merits further investigation. Our findings thus far suggest ECM supports tissue hyperplasia and altered metabolic demand following SBR.",
keywords = "Extracellular matrix, PPAR, Small bowel resection",
author = "Seiler, {Kristen M.} and Goo, {William H.} and Qiang Zhang and Cathleen Courtney and Adam Bajinting and Jun Guo and Warner, {Brad W.}",
note = "Funding Information: Acknowledgments: This work was supported by the Children's Discovery Institute of Washington University in St. Louis and St. Louis Children's Hospital MI-F-2017-629 (K.M.S.); the Children's Surgical Sciences Research Institute of the St. Louis Children's Hospital (B.W.W.); the Association for Academic Surgery Foundation (K.M.S.), National Institutes of Health 4T32HD043010-14 (K.M.S). Select histological analyses were performed with support from the Washington University Digestive Diseases Research Core Center. The mass spectrometric experiments were performed at the Washington University Proteomics Shared Resource (WU-PSR), Director, R Reid Townsend MD, PhD. The expert technical assistance of Petra Erdmann-Gilmore, Yiling Mi and Rose Connors is gratefully acknowledged. The WU-PSR is supported in part by the WU Institute of Clinical and Translational Sciences (NCATS UL1 TR000448), the Mass Spectrometry Research Resource (NIGMS P41 GM103422) and the Siteman Comprehensive Cancer Center Support Grant (NCI P30 CA091842). We thank the Genome Technology Access Center in the Department of Genetics at Washington University School of Medicine for help with genomic analysis. The Center is partially supported by NCI Cancer Center Support Grant #P30 CA91842 to the Siteman Cancer Center and by ICTS/CTSA Grant# UL1TR002345 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research. Publisher Copyright: {\textcopyright} 2020 Elsevier Inc.",
year = "2020",
month = jun,
doi = "10.1016/j.jpedsurg.2020.02.038",
language = "English",
volume = "55",
pages = "1107--1112",
journal = "Journal of Pediatric Surgery",
issn = "0022-3468",
number = "6",
}