Adaptation of Extracellular Matrix to Massive Small Bowel Resection in Mice

Overview

Journal J Pediatr Surg

Specialties General Surgery
Pediatrics

Date 2020 Mar 14

PMID 32164986

Citations 2

Authors

Kristen M Seiler

William H Goo

Qiang Zhang

Cathleen Courtney

Adam Bajinting

Jun Guo

Brad W Warner

Affiliations

Soon will be listed here.

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.

Level Of Evidence:

Citing Articles

Glucagon-like peptide-2 analogues for Crohn's disease patients with short bowel syndrome and intestinal failure.

Pizzoferrato M, Puca P, Ennas S, Cammarota G, Guidi L World J Gastroenterol. 2022; 28(44):6258-6270.

PMID: 36504557 PMC: 9730438. DOI: 10.3748/wjg.v28.i44.6258.

Distal Small Bowel Resection Yields Enhanced Intestinal and Colonic Adaptation.

Tecos M, Steinberger A, Guo J, Warner B J Surg Res. 2022; 273:100-109.

PMID: 35033819 PMC: 10364185. DOI: 10.1016/j.jss.2021.11.015.

References

Keller H, Devchand P, Perroud M, Wahli W . PPAR alpha structure-function relationships derived from species-specific differences in responsiveness to hypolipidemic agents. Biol Chem. 1997; 378(7):651-5. DOI: 10.1515/bchm.1997.378.7.651. View

Sukhotnik I, Roitburt A, Pollak Y, Dorfman T, Matter I, Mogilner J . Wnt/β-catenin signaling cascade down-regulation following massive small bowel resection in a rat. Pediatr Surg Int. 2013; 30(2):173-80. DOI: 10.1007/s00383-013-3447-9. View

Naba A, Clauser K, Lamar J, Carr S, Hynes R . Extracellular matrix signatures of human mammary carcinoma identify novel metastasis promoters. Elife. 2014; 3:e01308. PMC: 3944437. DOI: 10.7554/eLife.01308. View

Barron L, Sun R, Aladegbami B, Erwin C, Warner B, Guo J . Intestinal Epithelial-Specific mTORC1 Activation Enhances Intestinal Adaptation After Small Bowel Resection. Cell Mol Gastroenterol Hepatol. 2017; 3(2):231-244. PMC: 5331783. DOI: 10.1016/j.jcmgh.2016.10.006. View

Daley W, Peters S, Larsen M . Extracellular matrix dynamics in development and regenerative medicine. J Cell Sci. 2008; 121(Pt 3):255-64. DOI: 10.1242/jcs.006064. View

Kitano K, Schwartz D, Zhou H, Gilpin S, Wojtkiewicz G, Ren X . Bioengineering of functional human induced pluripotent stem cell-derived intestinal grafts. Nat Commun. 2017; 8(1):765. PMC: 5635127. DOI: 10.1038/s41467-017-00779-y. View

Dawson M, Xia Z . The retinoid X receptors and their ligands. Biochim Biophys Acta. 2011; 1821(1):21-56. PMC: 4097889. DOI: 10.1016/j.bbalip.2011.09.014. View

Aladegbami B, Barron L, Bao J, Colasanti J, Erwin C, Warner B . Epithelial cell specific Raptor is required for initiation of type 2 mucosal immunity in small intestine. Sci Rep. 2017; 7(1):5580. PMC: 5514129. DOI: 10.1038/s41598-017-06070-w. View

Brizzi M, Tarone G, Defilippi P . Extracellular matrix, integrins, and growth factors as tailors of the stem cell niche. Curr Opin Cell Biol. 2012; 24(5):645-51. DOI: 10.1016/j.ceb.2012.07.001. View

10.

Rakhshandehroo M, Knoch B, Muller M, Kersten S . Peroxisome proliferator-activated receptor alpha target genes. PPAR Res. 2010; 2010. PMC: 2948931. DOI: 10.1155/2010/612089. View

11.

Namachivayam K, MohanKumar K, Arbach D, Jagadeeswaran R, Jain S, Natarajan V . All-Trans Retinoic Acid Induces TGF-β2 in Intestinal Epithelial Cells via RhoA- and p38α MAPK-Mediated Activation of the Transcription Factor ATF2. PLoS One. 2015; 10(7):e0134003. PMC: 4520553. DOI: 10.1371/journal.pone.0134003. View

12.

Wang X, Harris R, Bayston L, Ashe H . Type IV collagens regulate BMP signalling in Drosophila. Nature. 2008; 455(7209):72-7. DOI: 10.1038/nature07214. View

13.

de Vogel-van den Bosch H, Bunger M, de Groot P, Bosch-Vermeulen H, Hooiveld G, Muller M . PPARalpha-mediated effects of dietary lipids on intestinal barrier gene expression. BMC Genomics. 2008; 9:231. PMC: 2408604. DOI: 10.1186/1471-2164-9-231. View

14.

Chandra V, Huang P, Hamuro Y, Raghuram S, Wang Y, Burris T . Structure of the intact PPAR-gamma-RXR- nuclear receptor complex on DNA. Nature. 2008; 456(7220):350-6. PMC: 2743566. DOI: 10.1038/nature07413. View

15.

Naba A, Clauser K, Hoersch S, Liu H, Carr S, Hynes R . The matrisome: in silico definition and in vivo characterization by proteomics of normal and tumor extracellular matrices. Mol Cell Proteomics. 2011; 11(4):M111.014647. PMC: 3322572. DOI: 10.1074/mcp.M111.014647. View

16.

Bunger M, van den Bosch H, van der Meijde J, Kersten S, Hooiveld G, Muller M . Genome-wide analysis of PPARalpha activation in murine small intestine. Physiol Genomics. 2007; 30(2):192-204. DOI: 10.1152/physiolgenomics.00198.2006. View

17.

Gajda A, Storch J . Enterocyte fatty acid-binding proteins (FABPs): different functions of liver and intestinal FABPs in the intestine. Prostaglandins Leukot Essent Fatty Acids. 2014; 93:9-16. PMC: 4323920. DOI: 10.1016/j.plefa.2014.10.001. View

18.

Perkins D, Pappin D, Creasy D, Cottrell J . Probability-based protein identification by searching sequence databases using mass spectrometry data. Electrophoresis. 1999; 20(18):3551-67. DOI: 10.1002/(SICI)1522-2683(19991201)20:18<3551::AID-ELPS3551>3.0.CO;2-2. View

19.

Zakany J, Darbellay F, Mascrez B, Necsulea A, Duboule D . Control of growth and gut maturation by genes and the associated lncRNA . Proc Natl Acad Sci U S A. 2017; 114(44):E9290-E9299. PMC: 5676926. DOI: 10.1073/pnas.1712511114. View

20.

Kramer A, Green J, Pollard Jr J, Tugendreich S . Causal analysis approaches in Ingenuity Pathway Analysis. Bioinformatics. 2013; 30(4):523-30. PMC: 3928520. DOI: 10.1093/bioinformatics/btt703. View