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miRNA Expression in Fibroblastic Foci within Idiopathic Pulmonary Fibrosis Lungs Reveals Novel Disease-Relevant Pathways

Lookup NU author(s): Laura Sabater, Jean-Baptiste Gossart, Inmaculada Hernandez Lopez, Dr Daniel Rico RodriguezORCiD, Dr Lee Borthwick, Professor Andrew FisherORCiD, Dr Joaquim Majo, Kasim Jiwa, Amy Collins, Giuseppe Abbate, Professor Fiona OakleyORCiD, Professor Derek Mann, Professor Jelena Mann



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


© 2023 American Society for Investigative PathologymiRNAs are 22 nucleotides long and belong to a class of noncoding RNAs that plays an important role in regulating gene expression at a post-transcriptional level. Studies show aberrant levels of miRNAs to be associated with profibrotic processes in idiopathic pulmonary fibrosis (IPF). However, most of these studies used whole IPF tissue or in vitro monocultures in which fibrosis was artificially induced. The current study used laser microdissection to collect fibroblastic foci (FF), the key pathologic lesion in IPF, isolated miRNAs, and compared their expression levels with those found in whole IPF lung tissue and/or in vitro cultured fibroblast from IPF or normal lungs. Sequencing libraries were generated, and data generated were bioinformatically analyzed. A total of 18 miRNAs were significantly overexpressed in FF tissue when compared with whole IPF tissue. Of those, 15 were unique to FF. Comparison of FF with cultured IPF fibroblasts also revealed differences in miRNA composition that impacted several signaling pathways. The miRNA composition of FF is both overlapping and distinct from that of whole IPF tissue or cultured IPF fibroblasts and highlights the importance of characterizing FF biology as a phenotypically and functionally discrete tissue microenvironment.

Publication metadata

Author(s): Sabater L, Gossart JB, Hernandez I, Rico D, Blanchard A, Borthwick LA, Fisher AJ, Majo J, Jiwa K, Collins A, Abbate G, Oakley F, Mann DA, Mann J

Publication type: Article

Publication status: Published

Journal: American Journal of Pathology

Year: 2023

Volume: 193

Issue: 4

Pages: 417-429

Print publication date: 01/04/2023

Online publication date: 20/01/2023

Acceptance date: 28/12/2022

Date deposited: 18/04/2023

ISSN (print): 0002-9440

ISSN (electronic): 1525-2191

Publisher: Elsevier Inc.


DOI: 10.1016/j.ajpath.2022.12.015

PubMed id: 36690076


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Funder referenceFunder name
206103/Z/17/ZWellcome Trust
MR/R023026/1Medical Research Council (MRC)