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Identifier 000451461
Title Role of RORa in fibroblast activation in Idiopathic Pulmonary Fibrosis
Alternative Title Ο ρόλος του RORa στην ενεργοποίηση των ινοβλαστών στην Ιδιοπαθή Πνευμονική Ίνωση
Author Ζέβλα, Δήμητρα Μαρία
Thesis advisor Αντωνίου, Κατερίνα
Reviewer Βεργίνης, Παναγιώτης
Τσατσάνης, Χρήστος
Abstract Idiopathic Pulmonary fibrosis (IPF) is a progressive, chronic, interstitial lung disease, characterized by irreversible lung fibrosis. Retinoic acid-related Orphan Receptor alpha (RORα; NR1F1) is a widely distributed nuclear receptor, involved in several (patho)physiological functions, including circadian rhythm, lipid metabolism, inflammation and angiogenesis. Members of the circadian clock BMAL1 and REVERBα, both transcriptionally regulated by RORα, have been previously shown to enhance and inhibit myofibroblast activation respectively. The role of RORα in pulmonary fibrosis remains unclear. To this end, we used human primary lung fibroblasts (HLFs) derived from surgical lung biopsies of lung cancer patients from areas of healthy tissue and from fibrotic areas from IPF patients. Our results showed that RORα knockdown significantly affected cytoskeletal and cell migration pathways demonstrated by transcriptomic analysis and a cell migration assay. Moreover, upregulation of pro-fibrotic genes such as α-SMA protein expression was observed. Similar results were observed following the treatment of HLFs with RORα antagonist R1001. We also evaluated the effect of TGFβ1 on RORα expression. Importantly, we detected a significant downregulation of RORα mRNA in HLFs following TGFβ1 treatment. Our results suggest that RORα plays a significant role in fibroblast activation and fibroblast to myofibroblast transition and is regulated by TGFβ1. We suggest that RORα, may represent a potential regulatory switch in IPF pathogenesis and a potential therapeutic target.
Language English
Subject Migration
Μετανάστευση
Issue date 2022-12-07
Collection   School/Department--School of Medicine--Department of Medicine--Post-graduate theses
  Type of Work--Post-graduate theses
Permanent Link https://elocus.lib.uoc.gr//dlib/e/9/9/metadata-dlib-1668586709-346676-5029.tkl Bookmark and Share
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