PU.1 controls fibroblast polarization and tissue fibrosis

Beitrag in einer Fachzeitschrift


Details zur Publikation

Autor(en): Wohlfahrt T, Rauber S, Uebe S, Luber M, Soare A, Ekici AB, Weber S, Matei AE, Chen CW, Maier C, Karouzakis E, Kiener HP, Pachera E, Dees C, Beyer C, Daniel C, Gelse K, Kremer A, Naschberger E, Stürzl M, Butter F, Sticherling M, Finotto S, Kreuter A, Kaplan MH, Jüngel A, Gay S, Nutt SL, Boykin DW, Poon GM, Distler O, Schett G, Distler J, Ramming A
Zeitschrift: Nature
Jahr der Veröffentlichung: 2019
ISSN: 0028-0836
eISSN: 1476-4687


Abstract

Fibroblasts are polymorphic cells with pleiotropic roles in organ morphogenesis, tissue homeostasis and immune responses. In fibrotic diseases, fibroblasts synthesize abundant amounts of extracellular matrix, which induces scarring and organ failure. By contrast, a hallmark feature of fibroblasts in arthritis is degradation of the extracellular matrix because of the release of metalloproteinases and degrading enzymes, and subsequent tissue destruction. The mechanisms that drive these functionally opposing pro-fibrotic and pro-inflammatory phenotypes of fibroblasts remain unknown. Here we identify the transcription factor PU.1 as an essential regulator of the pro-fibrotic gene expression program. The interplay between transcriptional and post-transcriptional mechanisms that normally control the expression of PU.1 expression is perturbed in various fibrotic diseases, resulting in the upregulation of PU.1, induction of fibrosis-associated gene sets and a phenotypic switch in extracellular matrix-producing pro-fibrotic fibroblasts. By contrast, pharmacological and genetic inactivation of PU.1 disrupts the fibrotic network and enables reprogramming of fibrotic fibroblasts into resting fibroblasts, leading to regression of fibrosis in several organs.


FAU-Autoren / FAU-Herausgeber

Beyer, Christian PD Dr.
Medizinische Klinik 3 - Rheumatologie und Immunologie
Daniel, Christoph Prof. Dr.
Nephropathologische Abteilung im Pathologischen Institut
Dees, Clara Dr. rer. nat.
Medizinische Klinik 3 - Rheumatologie und Immunologie
Distler, Jörg PD Dr.
Heisenberg-Professur für Molekulare Mechanismen der Organfibrose
Ekici, Arif Bülent Dr. rer. nat.
Humangenetisches Institut
Kremer, Andreas PD Dr.
Medizinische Klinik 1 - Gastroenterologie, Pneumologie und Endokrinologie
Maier, Christiane
Professur für Molekulare und Experimentelle Chirurgie
Matei, Alexandru-Emil Dr.
Medizinische Klinik 3 - Rheumatologie und Immunologie
Naschberger, Elisabeth PD Dr.
Medizinische Fakultät
Rauber, Simon
Medizinische Klinik 3 - Rheumatologie und Immunologie
Schett, Georg Prof. Dr. med.
Lehrstuhl für Innere Medizin III
Sticherling, Michael Prof. Dr.
Professur für Dermatologie
Stürzl, Michael Prof. Dr.
Professur für Molekulare und Experimentelle Chirurgie
Uebe, Steffen Dr. rer. nat.
Humangenetisches Institut
Weber, Stefanie
Medizinische Klinik 3 - Rheumatologie und Immunologie


Autor(en) der externen Einrichtung(en)
Carol Davila University of Medicine and Pharmacy / Universitatea de Medicină și Farmacie „Carol Davila” (UMF București)
Georgia State University
Indiana University – Purdue University Indianapolis
Institut für Molekulare Biologie gGmbH
Medizinische Universität Wien
Private Universität Witten/Herdecke gGmbH
Walter and Eliza Hall Institute of Medical Research (WEHI)


Zitierweisen

APA:
Wohlfahrt, T., Rauber, S., Uebe, S., Luber, M., Soare, A., Ekici, A.B.,... Ramming, A. (2019). PU.1 controls fibroblast polarization and tissue fibrosis. Nature. https://dx.doi.org/10.1038/s41586-019-0896-x

MLA:
Wohlfahrt, Thomas, et al. "PU.1 controls fibroblast polarization and tissue fibrosis." Nature (2019).

BibTeX: 

Zuletzt aktualisiert 2019-19-05 um 07:09