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Title: The role of mechano-growth factor in skeletal muscle injury
Authors: Sun, Keng Ting
Degree: Ph.D.
Issue Date: 2018
Abstract: Skeletal muscle regeneration is a well-orchestrated process involving regulated inflammatory response. Infiltrated myeloid cells, in particular macrophages, are implicated in the release of key soluble factors to modulate muscle inflammation. One such factor, insulin-like growth factor-1 (IGF-1) suppresses inflammatory cytokine expression and promotes anti-inflammatory macrophage polarization. However, IGF-1 exists in two isoforms and one of them IGF-1Ea was shown to be anti-inflammatory. Another isoform, mechano-growth factor (MGF) is structurally and functionally distinct from IGF-1Ea but it is unclear if MGF is implicated in muscle inflammation. In this thesis, we hypothesize that (i) the upregulation of MGF in injured muscle is associated with infiltration of myeloid cells including macrophages; and (ii) MGF can modulate inflammatory response during muscle injury. We first examined the transcription of MGF in response to cardiotoxin (CTX)-induced muscle injury in vivo. MGF upregulation correlated with that of inflammatory cytokines and coincided with myeloid cell infiltration. Furthermore, myeloid cells isolated at the time of MGF upregulation in injured muscles, including neutrophils and macrophages, expressed MGF. These findings suggested that MGF is associated with muscle inflammatory response, particularly the infiltration of myeloid cells. It prompted us to examine the roles of MGF in modulating muscle inflammatory response. We then investigated whether MGF could affect the expression of inflammatory markers and macrophage populations in muscle injury. At day 5, MGF overexpression led to upregulation of inflammatory markers which coincided with prolonged but transient increase of pro-inflammatory macrophages. The prolonged presence of macrophages might contribute to the inflammatory marker upregulation. Muscle resident cells were also implicated in the upregulation of these markers because MGF overexpression in the absence of CTX-induced injury could increase their expression level, yet in lower magnitude relative to the injury context. We then studied whether the modulation of inflammatory response by MGF overexpression translated into changes in muscle regeneration. The number and cross-sectional area of regenerating myofibers and the expression of regeneration-related transcripts were, nevertheless, not altered by MGF overexpression. This study highlights the roles of MGF in the expression of inflammatory markers and the modulation of macrophage resolution. The potential mechanisms of MGF in modulating inflammatory processes were discussed. To understand the role of MGF in muscle inflammation, future studies should examine the survival of pro-inflammatory macrophages. Although MGF expression did not seem to affect muscle regeneration outcomes, the current findings are novel and offer insights on the physiological roles of MGF in inflammatory response of muscle injury.
Subjects: Hong Kong Polytechnic University -- Dissertations
Muscles -- Wounds and injuries
Muscles -- Regeneration
Musculoskeletal system
Muscle cells
Pages: xx, 260 pages : color illustrations
Appears in Collections:Thesis

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