GSE122334 SPI1/PU.1 controls fibroblast polarization and tissue fibrosis

Contributors : Andreas Ramming ; Thomas Wohlfahrt ; Steffen Uebe ; Arif B EkiciSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensFibroblasts 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 sharp 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 have compared resting, fibrotic, and inflammatory fibroblasts; PU.1 was overexpressed in dermal fibroblasts and compared to scr-transfected controls. Fibrotic fibroblasts isolated from the skin of patients with systemic sclerosis were treated with PU.1 inhibitor and compared to untreated fibrotic fibroblasts and respective healthy controls.Through this, 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 fibrotic diseases such as pulmonary fibrosis, systemic sclerosis, liver cirrhosis, kidney fibrosis and chronic graft-versus-host disease, resulting in upregulation of...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Homo sapiens Source Type: research