Toggle Main Menu Toggle Search

Open Access padlockePrints

The Newcastle University research output collection, currently available on ePrints, will shortly be moving to a new open repository platform, Figshare. To prepare for the data migration we have paused adding new content to ePrints, and will resume once the new repository is launched. During this time you will continue to have access to ePrints (but no new content will appear). We will share updates here when available.

Long noncoding RNA H19X is a key mediator of TGF-β-driven fibrosis

Lookup NU author(s): Professor Fiona OakleyORCiD

Downloads

Full text for this publication is not currently held within this repository. Alternative links are provided below where available.

Abstract

© 2020, American Society for Clinical Investigation.TGF-β is a master regulator of fibrosis, driving the differentiation of fibroblasts into apoptosis-resistant myofibroblasts and sustaining the production of extracellular matrix (ECM) components. Here, we identified the nuclear long noncoding RNA (lncRNA) H19X as a master regulator of TGF-β-driven tissue fibrosis. H19X was consistently upregulated in a wide variety of human fibrotic tissues and diseases and was strongly induced by TGF-β, particularly in fibroblasts and fibroblast-related cells. Functional experiments following H19X silencing revealed that H19X was an obligatory factor for TGF-β-induced ECM synthesis as well as differentiation and survival of ECM-producing myofibroblasts. We showed that H19X regulates DDIT4L gene expression, specifically interacting with a region upstream of the DDIT4L gene and changing the chromatin accessibility of a DDIT4L enhancer. These events resulted in transcriptional repression of DDIT4L and, in turn, in increased collagen expression and fibrosis. Our results shed light on key effectors of TGF-β-induced ECM remodeling and fibrosis. Copyright:

Publication metadata

Author(s): Pachera E, Assassi S, Salazar GA, Stellato M, Renoux F, Wunderlin A, Blyszczuk P, Lafyatis R, Kurreeman F, De Vries-Bouwstra J, Messemaker T, Feghali-Bostwick CA, Rogler G, Van Haaften WT, Dijkstra G, Oakley F, Calcagni M, Schniering J, Maurer B, Distler JHW, Kania G, Frank-Bertoncelj M, Distler O

Publication type: Article

Publication status: Published

Journal: Journal of Clinical Investigation

Year: 2020

Volume: 130

Issue: 9

Pages: 4888-4905

Print publication date: 01/09/2020

Online publication date: 30/06/2020

Acceptance date: 17/06/2020

ISSN (print): 0021-9738

ISSN (electronic): 1558-8238

Publisher: American Society for Clinical Investigation

URL: https://doi.org/10.1172/JCI135439

DOI: 10.1172/JCI135439

PubMed id: 32603313

Altmetrics

Altmetrics provided by Altmetric

Share