Details

Autor(en) / Beteiligte

• Wohlfahrt, Thomas
• Rauber, Simon
• Uebe, Steffen
• Luber, Markus
• Soare, Alina
• Ekici, Arif
• Weber, Stefanie
• Matei, Alexandru-Emil
• Chen, Chih-Wei
• Maier, Christiane
• Karouzakis, Emmanuel
• Kiener, Hans P.
• Pachera, Elena
• Dees, Clara
• Beyer, Christian
• Daniel, Christoph
• Gelse, Kolja
• Kremer, Andreas E.
• Naschberger, Elisabeth
• Stürzl, Michael
• Butter, Falk
• Sticherling, Michael
• Finotto, Susetta
• Kreuter, Alexander
• Kaplan, Mark H.
• Jüngel, Astrid
• Gay, Steffen
• Nutt, Stephen L.
• Boykin, David W.
• Poon, Gregory M. K.
• Distler, Oliver
• Schett, Georg
• Distler, Jörg H. W.
• Ramming, Andreas

Titel

SPI1/PU.1 controls fibroblast polarization and tissue fibrosis

Ist Teil von

• Nature (London), 2019-01, Vol.566 (7744), p.344-349

Erscheinungsjahr

2019

Link zum Volltext

Beschreibungen/Notizen

• 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 lead to scaring and organ failure. In contrast, the hallmark feature of fibroblasts in arthritis is matrix degradation by the release of metalloproteinases and degrading enzymes, and subsequent tissue destruction. The mechanisms driving these functionally opposing pro-fibrotic and pro-inflammatory phenotypes of fibroblasts are enigmatic. We identified the transcription factor PU.1 as an essential orchestrator of the pro-fibrotic gene expression program. The interplay between transcriptional and post-transcriptional mechanisms which normally control PU.1 expression is perturbed in various fibrotic diseases, resulting in upregulation of PU.1, induction of fibrosis-associated gene sets, and a phenotypic switch in matrix-producing pro-fibrotic fibroblasts. In contrast, pharmacological and genetic inactivation of PU.1 disrupts the fibrotic network and enables re-programming of fibrotic fibroblasts into resting fibroblasts with regression of fibrosis in different organs.