| Title: |
Adipocyte associated glucocorticoid signaling regulates normal fibroblast function which is lost in inflammatory arthritis. |
| Authors: |
Faust, HJ; Cheng, T-Y; Korsunsky, I; Watts, GFM; Gal-Oz, ST; Trim, WV; Kongthong, S; Jonsson, AH; Simmons, DP; Zhang, F; Padera, R; Chubinskaya, S; Accelerating Medicines Partnership: RA/SLE Network; Wei, K; Raychaudhuri, S; Lynch, L; Moody, DB; Brenner, MB |
| Publisher Information: |
Springer Nature |
| Publication Year: |
2024 |
| Collection: |
Queen Mary University of London: Queen Mary Research Online (QMRO) |
| Subject Terms: |
Animals; Fibroblasts; Adipocytes; Signal Transduction; Receptors; Glucocorticoid; Mice; Synovial Membrane; Humans; Hydrocortisone; Glucocorticoids; Adipogenesis; 11-beta-Hydroxysteroid Dehydrogenase Type 1; Inbred C57BL; Knockout; Male; Transforming Growth Factor beta1; Arthritis; Tumor Necrosis Factor-alpha |
| Description: |
Fibroblasts play critical roles in tissue homeostasis, but in pathologic states they can drive fibrosis, inflammation, and tissue destruction. Little is known about what regulates the homeostatic functions of fibroblasts. Here, we perform RNA sequencing and identify a gene expression program in healthy synovial fibroblasts characterized by enhanced fatty acid metabolism and lipid transport. We identify cortisol as the key driver of the healthy fibroblast phenotype and that depletion of adipocytes, which express high levels of Hsd11b1, results in loss of the healthy fibroblast phenotype in mouse synovium. Additionally, fibroblast-specific glucocorticoid receptor Nr3c1 deletion in vivo leads to worsened arthritis. Cortisol signaling in fibroblasts mitigates matrix remodeling induced by TNF and TGF-β1 in vitro, while stimulation with these cytokines represses cortisol signaling and adipogenesis. Together, these findings demonstrate the importance of adipocytes and cortisol signaling in driving the healthy synovial fibroblast state that is lost in disease. |
| Document Type: |
article in journal/newspaper |
| File Description: |
9859 - ? |
| Language: |
English |
| Relation: |
Nat Commun; https://qmro.qmul.ac.uk/xmlui/handle/123456789/104409 |
| DOI: |
10.1038/s41467-024-52586-x |
| Availability: |
https://qmro.qmul.ac.uk/xmlui/handle/123456789/104409; https://doi.org/10.1038/s41467-024-52586-x |
| Rights: |
This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/. ; © The Author(s) 2024 |
| Accession Number: |
edsbas.88ECEE5B |
| Database: |
BASE |