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The effect of mechanical load on dermal fibroblast collagen deposition and organisation

Parsons, Madeline; (1999) The effect of mechanical load on dermal fibroblast collagen deposition and organisation. Doctoral thesis (Ph.D), UCL (University College London). Green open access

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During dermal wound healing, resident cells are constantly exposed to mechanical forces from surrounding tissue movement. It is hypothesised that these forces contribute to increased human dermal fibroblast collagen deposition and alignment, and that this external mechanical signal is transduced to the cell nucleus via the cell surface receptors integrins. To address this hypothesis, two in vitro mechanical loading systems have been employed: a 2-dimensional system to load dermal fibroblasts in monolayer culture and a 3-dimensional system to load cells within a collagen gel. The effect of mechanical load in the presence of serum or growth factors on procollagen synthesis and deposition was determined in each system. It was found that mechanical load alone in either system had no effect on procollagen synthesis. However, in the presence of 10% fetal calf serum or TGFB, both loading regimens lead to a highly significant stimulation of procollagen synthesis. Levels of the enzyme procollagen c-proteinase, critical in the formation of insoluble collagen fibrils, were also increased in response to load, whereas the procollagen c-proteinase enhancer protein was not. In the 3-dimensional system there was also alignment of collagen fibrils in response to load, and this was shown to be dependent on the load-induced increase in collagen synthesis. The involvement of integrins in load-induced procollagen synthesis in the 2-dimensional system was investigated. Integrin α1β1 was shown to be increased at the cell surface in loaded cultures, and important in basal procollagen synthesis. α2β1 was transiently increased at the cell surface by mechanical load, and was specifically involved in mediating load-induced collagen synthesis and deposition. α5βl was not involved in collagen synthesis is this system. These data demonstrate that mechanical load and growth factors act synergistically to enhance human dermal fibroblast collagen synthesis, deposition and re-organisation, and that these phenomena are in part regulated by specific integrins. The elucidation of these mechanisms has furthered the understanding of fibroblast responses to mechanical load, and may assist in the development of novel therapeutic strategies to treat pathologies involving enhanced dermal scarring.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: The effect of mechanical load on dermal fibroblast collagen deposition and organisation
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest.
Keywords: Biological sciences; Dermal healing
URI: https://discovery.ucl.ac.uk/id/eprint/10107099
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