Journal article
PU.1 controls fibroblast polarization and tissue fibrosis
T Wohlfahrt, S Rauber, S Uebe, M Luber, A Soare, A Ekici, S Weber, AE Matei, CW Chen, C Maier, E Karouzakis, HP Kiener, E Pachera, C Dees, C Beyer, C Daniel, K Gelse, AE Kremer, E Naschberger, M Stürzl Show all
Nature | NATURE PORTFOLIO | Published : 2019
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 prog..
View full abstractGrants
Awarded by National Institutes of Health
Funding Acknowledgements
We thank M. Pascual, K. Dreissigacker, K.-T. Yang, R. Kleinlein and M. Spiller-Becker for technical assistance; and R. Palmisano and P. Tripal of the Optical Imaging Center Erlangen (OICE) for helping with confocal images. This work was supported by grants RA 2506/3-1, RA 2506/4-1, DI 1537/9-1, DI 1537/11-1, DE 2414/2-1, AK 144/2-1, DFG FOR2438, SCHE 1583/7-1, SPP1468, CRC1181 (A01, C01) and SFB TR221 (B04) of the German Research Foundation, the Bundesministerium fur Bildung und Forschung (BMBF; project Metharthros), the Marie Curie project OSTEOIMMUNE, the TEAM project of the European Union (305549) and the IMI funded project RTCure (115142), Else Kroner-Fresenius-Stiftung 2014_A184, grants A64, D28 and J40 of the IZKF in Erlangen, grant 16-10-05-1-Ramming of the ELAN-Foundation Erlangen, grant 2017.129.1 of the Wilhelm Sander-Stiftung, grant SNF310030_166259 (to O.D.), NIH (R01 A1057459 and AI095282 to M.H.K.; H1.129063 to G.M.K.P.).