The role of microRNA-155 as a master switch determining the balance of inflammation and fibrosis in chronic disorders

Morton, Brian Edward (2018) The role of microRNA-155 as a master switch determining the balance of inflammation and fibrosis in chronic disorders. PhD thesis, University of Glasgow.

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Macrophages are a dynamic cell type and represent a key component of the immune response, with a broad range of activities throughout the body. They respond to external cues, including microbes, alarmins, and growth factors, to eliminate invading pathogens through initiation of inflammation. Subsequently, they carry out several regulatory roles, including clearance of cellular debris, the resolution of inflammation, and wound healing to restore tissue homeostasis after an inflammatory response. The ability of macrophages to change their phenotype in this manner must be tightly regulated, as dysregulated macrophage activity is central to the pathogenesis of both inflammatory and fibrotic autoimmune disorders, such as Rheumatoid Arthritis (RA) and Idiopathic Pulmonary Fibrosis (IPF), respectively. One of the mechanisms by which regulation of macrophages occurs is the microRNA network.
MicroRNAs (miRNAs) are a class of short, non-protein coding RNAs that post-transcriptionally regulate gene expression through translational repression, destabilisation or degradation of target mRNA. miR-155 is a multi-functional miRNA that has roles in regulating the development and function of many immune cells, including macrophages. Abnormal expression of miR-155 is associated with a number of autoimmune disorders and cancers. We reported previously that miR-155 is elevated in RA and contributes to the chronic, pro- inflammatory response of macrophages by repressing key anti-inflammatory proteins. However, the role of miR-155 in the regulation of remodelling responses by macrophages is less well characterised.
Modulation of miRNA activity in cells through the use of mimics and inhibitors has emerged as a potential therapeutic strategy for the treatment of diseases. Technologies involving the use of lipid vesicles as delivery agents for introducing therapeutics into target cells have shown potential in increasing the drug efficacy.

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Additional Information: Due to copyright restrictions the full text of this thesis cannot be made available online. Access to the printed version is available once any embargo periods have expired.
Keywords: microRNA, miR-155, inflammation, fibrosis, macrophage, rheumatoid arthritis, idiopathic pulmonary fibrosis.
Subjects: Q Science > QR Microbiology
Colleges/Schools: College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation > Immunology
Supervisor's Name: Kurowska-Stolarska, Dr. M. and McInnes, Professor I.B.
Date of Award: 2018
Embargo Date: 13 June 2021
Depositing User: Mr Brian Morton
Unique ID: glathesis:2018-9118
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 13 Jun 2018 09:40
Last Modified: 16 Jul 2018 08:56

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