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Massey Dolin Hepatology 2017 Hepatic matrisome response to injury

ABSTRACT: Proteomic analysis of mouse livers from animals maintained on 6-week diet of alcohol with a 10mg/kg ip LPS or saline (control) injection 24hr prior to sacrifice. Livers were extracted using a sequential extraction approach similiar to the method of de Castro Bras LE, Ramirez TA, DeLeon-Pennell KY, Chiao YA, Ma Y, Dai Q, et al. Texas 3-step decellularization protocol: looking at the cardiac extracellular matrix. J Proteomics 2013;86:43-52. Data collection and analysis are described in Massey VL, Dolin CE, Poole LG, Hudson SV, Siow DL, Brock GN, Merchant ML, Wilkey DW, Arteel GE. The hepatic "matrisome" responds dynamically to injury: Characterization of transitional changes to the extracellular matrix in mice. Hepatology. 2017 Mar;65(3):969-982. doi: 10.1002/hep.28918. Epub 2016 Dec 30. PubMed PMID: 28035785; PubMed Central PMCID: PMC5319876.

INSTRUMENT(S): LTQ Orbitrap Elite

ORGANISM(S): Mus <mouse, Genus> (ncbitaxon:10088)

SUBMITTER: Gavin Arteel, PhD

PROVIDER: MSV000081084 | MassIVE | Mon May 15 09:36:00 BST 2017

SECONDARY ACCESSION(S): PXD006521

REPOSITORIES: MassIVE

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Project description:In this project we aimed at deciphering modulation in genes expression induced by external pulsed electric fields applied in reversible electroporation-based treatments. Thanks to their local application and transient effects, physical stimuli appear as attractive tools to remodel extracellular matrix, which was the point of interest in our to be published study. We assessed the potential of pulsed electric field technology, classically applied to drug delivery, to induce collagen remodeling at the tissue scale. A sophisticated in vitro tissue-engineered human dermal substitute, a tissue model rich in endogeneous extracellular matrix such as collagens, was used to demonstrate the effects of microsecond and millisecond pulsed electric fields applied respectively in electrochemotherapy (ECT) treatment and gene electrotransfer (GET) strategy. Our analyses, focused on matrisome genes and extracellular matrix remodeling, underpin that pulsed electric fields, a technology already approved for clinical use combined with anti-cancer agents, are particularly promising to provide local and effective treatment of abnormal extracellular matrix. Part of this dataset was used to describe how pulsed electric field on its own (with no addition of external drugs) induce extracellular matrix (ECM) remodeling at human dermal scale, by focusing at genes related to matrisome subset. In this manuscript to be published, electrochemotherapy (ECT) parameters were named SP for "short pulses" and gene electrotransfer (GET) parameters were named LP for "long pulses". W demonstrated that these both types of electric parameters inducing reversible electroporation of the cells whitin the dermal tissue substitute induced 1) a rapid modulation (4h after electrostimulation) of mRNA’s genes composing the matrisome, particularly a down-regulation of pro-collagens and ECM maturation’s enzymes such as transglutaminase TG2 and LOX-like; 2) a transient decrease in pro-collagens production and hydroxyproline tissue content within a week after electrostimulation; 3) a long-lasting ROS-dependent over-activation of MMPs for at least 48h and 4) a down-regulation at both mRNA and protein level of pro-fibrotic TGF-β.

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Massey Dolin Hepatology 2017 Hepatic matrisome response to injury

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