Attenuation of Dupuytren's fibrosis via targeting of the STAT1 modulated IL-13Rα1 response.

Science Advances
Moeed AkbarNeal L Millar

Abstract

Fibrotic disorders represent common complex disease pathologies that are therapeutically challenging. Inflammation is associated with numerous fibrotic pathogeneses; however, its role in the multifaceted mechanisms of fibrosis remains unclear. IL-13 is implicated in aberrant responses involved in fibrotic disease, and we aimed to understand its role in the inflammatory processes of a common fibrotic disorder, Dupuytren's disease. We demonstrated T-cells produced IFN-g, which induced IL-13 secretion from mast cells and up-regulated IL-13Ra1 on fibroblasts, rendering them more reactive to IL-13. Consequently, diseased myofibroblasts demonstrated enhanced fibroproliferative effects upon IL-13 stimulation. We established IFN-g and IL-13 responses involved STAT dependent pathways, and STAT targeting (tofacitinib) could inhibit IL-13 production from mast cells, IL-13Ra1 up-regulation in fibroblasts and fibroproliferative effects of IL-13 on diseased myofibroblasts. Accordingly, utilizing Dupuytren's as an accessible human model of fibrosis, we propose targeting STAT pathways may offer previously unidentified therapeutic approaches in the management of fibrotic disease.

References

Aug 1, 1991·The Journal of Hand Surgery : Journal of the British Society for Surgery of the Hand·J G AndrewB Turner
Apr 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·A N McKenzieS Menon
Feb 3, 1998·American Journal of Respiratory Cell and Molecular Biology·A HancockA Millar
May 29, 1998·The Journal of Clinical Investigation·C DoucetB Azzarone
Jan 14, 1999·The Journal of Investigative Dermatology·S J ChenJ Varga
Aug 27, 1999·The Journal of Bone and Joint Surgery. British Volume·R M MeekJ F Crossan
Dec 14, 1999·Kidney International·S D OldroydA M El Nahas
May 15, 2001·American Journal of Respiratory Cell and Molecular Biology·E S ChenD R Moller
Jan 24, 2002·American Journal of Physiology. Gastrointestinal and Liver Physiology·Hirotada AkihoStephen M Collins
Sep 5, 2002·Nature Reviews. Molecular Cell Biology·Mark E Fortini
Jun 6, 2003·Journal of Dermatological Science·Toshio HasegawaHideoki Ogawa
Nov 9, 2004·Immunologic Research·Claudia JakubzickCory M Hogaboam
Oct 20, 2005·Clinical Gastroenterology and Hepatology : the Official Clinical Practice Journal of the American Gastroenterological Association·Hong-Lei WengSteven Dooley
Oct 13, 2006·The Journal of Allergy and Clinical Immunology·Allison-Lynn AndrewsDonna E Davies
Feb 15, 2007·The Journal of Investigative Dermatology·Boris Hinz
Mar 3, 2007·The Journal of Clinical Investigation·Thomas A Wynn
Mar 6, 2007·The Journal of Hand Surgery·Phillip JohnstonIan M Clark
May 17, 2007·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Nicholas J LapingCheryl L Walker
Apr 2, 2009·Nature Reviews. Rheumatology·John Varga, Boris Pasche
Jan 1, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Andrew L RankinStefan Pflanz
Mar 9, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Kamran GhoreschiJohn J O'Shea
Jul 8, 2011·The New England Journal of Medicine·Guido H DolmansUNKNOWN BSSH-GODD Consortium
Jul 9, 2011·The Journal of Clinical Investigation·Mang YuStephen J Galli
Aug 24, 2011·Toxicologic Pathology·Mark J AndertonAnnabelle Heier
Oct 6, 2011·Annals of the Rheumatic Diseases·Neal L MillarIain B McInnes
Feb 23, 2013·Proceedings of the National Academy of Sciences of the United States of America·Liaquat S VerjeeJagdeep Nanchahal
Nov 16, 2014·Annals of the Rheumatic Diseases·D L BoyleG S Firestein
Feb 24, 2015·Pharmacological Reviews·Stefan SiebertIain McInnes
Jun 3, 2015·Journal of the American Society of Nephrology : JASN·Jingyin YanYanlin Wang
Apr 26, 2016·Nature Reviews. Nephrology·Xiao-Ming MengHui Yao Lan
Apr 30, 2016·The Journal of Pathology·Thirumalai R RamalingamThomas A Wynn
Jun 4, 2016·Nature Communications·Swati BhattacharyyaJohn Varga
Jul 2, 2016·Fibrogenesis & Tissue Repair·Marike M van BeugeRuud A Bank
Aug 19, 2016·United European Gastroenterology Journal·Noam JacobDavid Q Shih
Mar 3, 2017·Nature Reviews. Rheumatology·Kevin L Winthrop
Aug 5, 2017·Frontiers in Pharmacology·Kelly L WaltonCraig A Harrison

❮ Previous
Next ❯

Citations

Jul 30, 2020·Nature Reviews. Rheumatology·Jessica McHugh

❮ Previous
Next ❯

Methods Mentioned

BETA
immunoprecipitation
flow cytometry
ChIP
xenograft
enzyme-linked immunosorbent assay

Software Mentioned

DIVA
GraphPad Prism

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.

Related Papers

Arerugī = [Allergy]
Hepatology : Official Journal of the American Association for the Study of Liver Diseases
Monica ChiaramonteThomas A Wynn
The Journal of Allergy and Clinical Immunology
Gurjit K Khurana Hershey
Annual Review of Immunology
Thomas A Wynn
© 2021 Meta ULC. All rights reserved