Bibliographic Details
| Title: |
PU.1 controls fibroblast polarization and tissue fibrosis. |
| Authors: |
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 |
| Source: |
Nature; 2/21/2019, Vol. 566 Issue 7744, p344-349, 6p, 14 Graphs |
| 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. The transcription factor PU.1 is an essential regulator of the pro-fibrotic gene expression program in fibroblasts; PU.1 expression is upregulated in various fibrotic diseases, whereas inactivation of PU.1 induces regression of fibrosis in a number of organs. [ABSTRACT FROM AUTHOR] |
|
Copyright of Nature is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) |
| Database: |
Complementary Index |
