Syndecan-1 promotes lung fibrosis by regulating epithelial reprogramming through extracellular vesicles.

JCI Insight
Tanyalak ParimonPeter Chen

Abstract

Idiopathic pulmonary fibrosis (IPF) is a chronic and fatal lung disease. A maladaptive epithelium due to chronic injury is a prominent feature and contributor to pathogenic cellular communication in IPF. Recent data highlight the concept of a "reprogrammed" lung epithelium as critical in the development of lung fibrosis. Extracellular vesicles (EVs) are potent mediator of cellular crosstalk, and recent evidence supports their role in lung pathologies such as IPF. Here, we demonstrate that syndecan-1 is overexpressed by the epithelium in the lungs of IPF patients and in murine models after bleomycin injury. Moreover, we find that syndecan-1 is a pro-fibrotic signal that alters alveolar type II (ATII) cell phenotypes by augmenting TGFβ and Wnt signaling among other pro-fibrotic pathways. Importantly, we demonstrate that syndecan-1 controls the packaging of several anti-fibrotic microRNAs into EVs that have broad effects over several fibrogenic signaling networks as a mechanism of regulating epithelial plasticity and pulmonary fibrosis. Collectively, our work reveals new insight into how EVs orchestrate cellular signals that promote lung fibrosis and demonstrate the importance of syndecan-1 in coordinating these programs.

References

Jul 11, 2000·Nature Genetics·C M AlexanderM Bernfield
Apr 23, 2003·The American Journal of Pathology·Marco ChilosiClaudio Doglioni
Aug 23, 2006·Proceedings of the National Academy of Sciences of the United States of America·Kevin K KimHarold A Chapman
Aug 11, 2007·Science·Hongjun LiuToren Finkel
May 15, 2008·PloS One·Melanie KönigshoffOliver Eickelberg
Nov 4, 2008·Nature·Donny D LicatalosiRobert B Darnell
Oct 24, 2009·American Journal of Respiratory and Critical Care Medicine·Thomas H SissonRichard H Simon
Oct 12, 2010·American Journal of Respiratory and Critical Care Medicine·Brett LeyTalmadge E King
Jan 15, 2011·Source Code for Biology and Medicine·Guorong XuDongxiao Zhu
Apr 22, 2011·The New England Journal of Medicine·Max A SeiboldDavid A Schwartz
Jun 10, 2011·Proceedings of the American Thoracic Society·Zea BorokDeborah Hoshizaki
Oct 4, 2011·Cell·Hao ZhuGeorge Q Daley
Oct 26, 2011·The Journal of Cell Biology·Nam Hee KimJong In Yook
Oct 29, 2011·Matrix Biology : Journal of the International Society for Matrix Biology·Yvonne Hui-Fang TengPyong Woo Park
Jun 5, 2012·Nature Cell Biology·Maria Francesca BaiettiGuido David
Jul 10, 2012·Nature Medicine·Thomas A Wynn, Thirumalai R Ramalingam
Aug 18, 2012·Journal of Cell Science·William A AltemeierPeter Chen
Jan 25, 2013·Molecular Therapy. Nucleic Acids·Mehmet Fatih BolukbasiOkay Saydam
Feb 20, 2013·The Journal of Cell Biology·Graça Raposo, Willem Stoorvogel
May 23, 2013·The New England Journal of Medicine·Gary M HunninghakeDavid A Schwartz
Oct 29, 2013·American Journal of Respiratory and Critical Care Medicine·Timothy S BlackwellJerry P Eu
Dec 18, 2013·Bioinformatics·Andreas KrämerStuart Tugendreich
Dec 21, 2013·Nature Communications·Carolina Villarroya-BeltriFrancisco Sánchez-Madrid
Mar 20, 2014·American Journal of Respiratory and Critical Care Medicine·Moisés Selman, Annie Pardo
Sep 23, 2014·Cell Reports·Danijela Koppers-LalicD Michiel Pegtel
Oct 26, 2014·Development·Katsufumi DejimaAndrew D Chisholm
Dec 18, 2014·Genome Biology·Michael I LoveSimon Anders
Mar 4, 2015·Cell Research·Bart RoucourtGuido David
Apr 4, 2015·The European Respiratory Journal·Jonathan A KropskiJames E Loyd
Apr 8, 2015·The Journal of Experimental Medicine·Emilie BourdonnayMarc Peters-Golden
Jul 7, 2015·Cell Reports·Juan M PovedanoMaria A Blasco

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Citations

May 14, 2020·Allergy, Asthma & Immunology Research·Min Gyu KangHeung Woo Park
Mar 27, 2020·Scientific Reports·Eric A EvangelistaSina A Gharib
Mar 29, 2020·International Journal of Molecular Sciences·Tanyalak ParimonPeter Chen
Apr 13, 2021·Frontiers in Pharmacology·Pamela Velázquez-DíazYang Zhou

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Datasets Mentioned

BETA
GSE134948
GSE134741
GSE131800

Methods Mentioned

BETA
scRNA-Seq
RNA-Seq
pull-down
HITS-CLIP
bronchoalveolar lavage
transfect
transfections
protein assay
PCR
flow cytometry

Software Mentioned

CellRanger
Ingenuity Pathway Analysis
Seurat package
CITE
DESeq2
TopHat2
Partek Flow
Webgestaldt
Ensembl
Seurat

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