Transcriptome analysis of IPF fibroblastic foci identifies key pathways involved in fibrogenesis.

Thorax
Delphine GuillotinRachel C Chambers

Abstract

Fibroblastic foci represent the cardinal pathogenic lesion in idiopathic pulmonary fibrosis (IPF) and comprise activated fibroblasts and myofibroblasts, the key effector cells responsible for dysregulated extracellular matrix deposition in multiple fibrotic conditions. The aim of this study was to define the major transcriptional programmes involved in fibrogenesis in IPF by profiling unmanipulated myofibroblasts within fibrotic foci in situ by laser capture microdissection. The challenges associated with deriving gene calls from low amounts of RNA and the absence of a meaningful comparator cell type were overcome by adopting novel data mining strategies and by using weighted gene co-expression network analysis (WGCNA), as well as an eigengene-based approach to identify transcriptional signatures, which correlate with fibrillar collagen gene expression. WGCNA identified prominent clusters of genes associated with cell cycle, inflammation/differentiation, translation and cytoskeleton/cell adhesion. Collagen eigengene analysis revealed that transforming growth factor β1 (TGF-β1), RhoA kinase and the TSC2/RHEB axis formed major signalling clusters associated with collagen gene expression. Functional studies using CRISPR-Cas9 gene-...Continue Reading

References

Sep 9, 1998·American Journal of Respiratory Cell and Molecular Biology·R C ChambersG Westergren-Thorsson
Jun 13, 2002·Proceedings of the National Academy of Sciences of the United States of America·M Girvan, M E J Newman
Jul 18, 2002·American Journal of Respiratory and Critical Care Medicine·Andrew G NicholsonAthol U Wells
Mar 3, 2007·The Journal of Clinical Investigation·Thomas A Wynn
Jul 31, 2007·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Ahmed M Elsharkawy, Derek A Mann
Aug 2, 2007·Mammalian Genome : Official Journal of the International Mammalian Genome Society·Tova F FullerSteve Horvath
Dec 19, 2007·The Journal of Cell Biology·Pierre-Jean WipffBoris Hinz
Mar 18, 2008·European Journal of Cell Biology·Pierre-Jean Wipff, Boris Hinz
Dec 31, 2008·BMC Bioinformatics·Peter Langfelder, Steve Horvath
Aug 5, 2009·The Journal of Clinical Investigation·Chris J ScottonRachel C Chambers
Feb 5, 2011·Nature Reviews. Gastroenterology & Hepatology·Tom Luedde, Robert F Schwabe
Mar 18, 2011·EMBO Molecular Medicine·Nicole A Neuman, Elizabeth Petri Henske
Apr 8, 2011·American Journal of Respiratory and Critical Care Medicine·Ganesh RaghuUNKNOWN ATS/ERS/JRS/ALAT Committee on Idiopathic Pulmonary Fibrosis
Jun 12, 2012·EMBO Molecular Medicine·Robert J J O'DonoghueSteven E Mutsaers
Nov 26, 2013·Biochimica Et Biophysica Acta·Sabrina CavinDario Diviani
May 20, 2014·The New England Journal of Medicine·Talmadge E KingUNKNOWN ASCEND Study Group
Jul 17, 2014·American Journal of Respiratory Cell and Molecular Biology·Yasmina BauerNaftali Kaminski
Sep 26, 2014·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Aravind T ReddyRaju C Reddy
Dec 2, 2015·Respiratory Research·Su Su HtweAmir M Ghaemmaghami
Mar 12, 2017·Cell·Robert A Saxton, David M Sabatini
Sep 30, 2017·Nature Methods·Susanne C van den BrinkAlexander van Oudenaarden
Jan 3, 2018·The Journal of Clinical Investigation·Mitsuo YamauchiJonathan M Kurie
Feb 25, 2018·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Mi-Yeon JungEdward B Leof
Apr 20, 2018·Frontiers in Medicine·Milica Vukmirovic, Naftali Kaminski
Dec 18, 2018·American Journal of Respiratory and Critical Care Medicine·Paul A ReyfmanAlexander V Misharin
Jan 4, 2019·Nature Communications·Hannah V WoodcockRachel C Chambers
Jan 12, 2019·Expert Review of Respiratory Medicine·Lykourgos KolilekasDemosthenes Bouros
Oct 1, 2019·Expert Review of Respiratory Medicine·Amornpun WongkarnjanaMartin Rj Kolb

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