Exploratory descriptive study of the support tissue in keloids

Keloids are benign hyper-proliferative growths of fibrous tissue, where increased fibroblast activity results in abnormal collagen deposition. Scientific literature related to the morphological features of keloids especially at an ultrastructural level is outdated. Therefore the aim of this study...

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Main Author: Arbi, Sandra
Other Authors: Bester, Megan J.
Language:en
Published: University of Pretoria 2015
Subjects:
Online Access:http://hdl.handle.net/2263/45920
Arbi, S 2014, Exploratory descriptive study of the support tissue in keloids, MSc Dissertation, University of Pretoria, Pretoria, viewed yymmdd <http://hdl.handle.net/2263/45920>
id ndltd-netd.ac.za-oai-union.ndltd.org-up-oai-repository.up.ac.za-2263-45920
record_format oai_dc
collection NDLTD
language en
sources NDLTD
topic Keloid
Collagen
Fibre
Fibrddast
Must cell
UCTD
spellingShingle Keloid
Collagen
Fibre
Fibrddast
Must cell
UCTD
Arbi, Sandra
Exploratory descriptive study of the support tissue in keloids
description Keloids are benign hyper-proliferative growths of fibrous tissue, where increased fibroblast activity results in abnormal collagen deposition. Scientific literature related to the morphological features of keloids especially at an ultrastructural level is outdated. Therefore the aim of this study was to reassess present knowledge of the ultrastructural features of keloids and possibly through this process identify new cellular therapeutic targets. The research was conducted on normal (control) and keloid human skin samples collected from consenting patients undergoing keloid removal and skin transplantation surgeries at the Steve Biko Academic Hospital. The tissue structure of normal/control skin and keloids as well as mast cell and collagen distribution were evaluated using histological techniques. Transmission electron microscopy techniques were undertaken in order to investigate morphological and ultrastructural features of cells of the epidermis and dermis. A further detailed analysis of the ultrastructure of keloid fibroblasts and mast cells was undertaken. The findings of this study have lead to a new hypothesis related to keloid formation. Increased fibroblast activity, intracellular collagen production and fibroblast and mast cell interactions were seen in keloid tissue. Changes in the morphology of keratinocytes and melanocytes were observed, where the cytoplasmic processes of both cells were shorter and cells were packed closer together in keloids. Keloid tissue appeared to be in a hyperproliferative state similar to that of the granulation phase of wound healing. Increased amounts of collagen were found in the extracellular matrix (ECM) of keloid tissue. This is the first study in which the abnormal accumulation of insoluble collagen fibrils was observed in the cytoplasm. Degranulation of mast cells had occurred and these cells were found in close association with fibroblasts. In some instances phagocytosis of collagen by mast cells was also observed. These observations have led to the hypothesis that transforming growth factor β (TGF-β) derived from mast cells, inhibits keratinocyte proliferation and stimulates increased collagen production through increased expression of lysyl oxidase (LOX) by fibroblasts. Intracellular insoluble collagen formation then occurs due to the rapid, intracellular removal of the C terminal pro-peptide sequence by C-proteinase which initiates the cascade of insoluble collagen fibre formation within the fibroblast. Normally this process occurs only within the ECM in response to the increasing mass of collagen and in an attempt to establish normal tissue homeostasis the mast cells engulf the bundles of collagen fibres. Increased stress on the epidermal layer causes increased keratinocyte proliferation, which results in further growth factor mediated replication of fibroblasts. This creates an endless cycle of collagen synthesis, mast cell degranulation and mast cell mediated collagen phagocytosis, physical stress on the epidermal layer and subsequent growth factor release and fibroblast activation, collagen synthesis and subsequent crowding of keratinocytes and melanocytes. In conclusion, this study identified keloid formation as a defect of procollagen synthesis and processing. Phagocytosis of collagen by mast cells indicates that accumulation of these cells may be a secondary effect to excessive collagen synthesis. In addition, the release of interleukins, mediators and growth factors may further stimulate collagen fibril formation with the imbalance toward increased synthesis. This study also identified and confirmed the findings of other studies that procollagen C-proteinase is an important therapeutic target. === Dissertation (MSc)--University of Pretoria, 2014. === tm2015 === Anatomy === MSc === Unrestricted
author2 Bester, Megan J.
author_facet Bester, Megan J.
Arbi, Sandra
author Arbi, Sandra
author_sort Arbi, Sandra
title Exploratory descriptive study of the support tissue in keloids
title_short Exploratory descriptive study of the support tissue in keloids
title_full Exploratory descriptive study of the support tissue in keloids
title_fullStr Exploratory descriptive study of the support tissue in keloids
title_full_unstemmed Exploratory descriptive study of the support tissue in keloids
title_sort exploratory descriptive study of the support tissue in keloids
publisher University of Pretoria
publishDate 2015
url http://hdl.handle.net/2263/45920
Arbi, S 2014, Exploratory descriptive study of the support tissue in keloids, MSc Dissertation, University of Pretoria, Pretoria, viewed yymmdd <http://hdl.handle.net/2263/45920>
work_keys_str_mv AT arbisandra exploratorydescriptivestudyofthesupporttissueinkeloids
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spelling ndltd-netd.ac.za-oai-union.ndltd.org-up-oai-repository.up.ac.za-2263-459202020-06-02T03:18:20Z Exploratory descriptive study of the support tissue in keloids Arbi, Sandra Bester, Megan J. Taute, Helena Keloid Collagen Fibre Fibrddast Must cell UCTD Keloids are benign hyper-proliferative growths of fibrous tissue, where increased fibroblast activity results in abnormal collagen deposition. Scientific literature related to the morphological features of keloids especially at an ultrastructural level is outdated. Therefore the aim of this study was to reassess present knowledge of the ultrastructural features of keloids and possibly through this process identify new cellular therapeutic targets. The research was conducted on normal (control) and keloid human skin samples collected from consenting patients undergoing keloid removal and skin transplantation surgeries at the Steve Biko Academic Hospital. The tissue structure of normal/control skin and keloids as well as mast cell and collagen distribution were evaluated using histological techniques. Transmission electron microscopy techniques were undertaken in order to investigate morphological and ultrastructural features of cells of the epidermis and dermis. A further detailed analysis of the ultrastructure of keloid fibroblasts and mast cells was undertaken. The findings of this study have lead to a new hypothesis related to keloid formation. Increased fibroblast activity, intracellular collagen production and fibroblast and mast cell interactions were seen in keloid tissue. Changes in the morphology of keratinocytes and melanocytes were observed, where the cytoplasmic processes of both cells were shorter and cells were packed closer together in keloids. Keloid tissue appeared to be in a hyperproliferative state similar to that of the granulation phase of wound healing. Increased amounts of collagen were found in the extracellular matrix (ECM) of keloid tissue. This is the first study in which the abnormal accumulation of insoluble collagen fibrils was observed in the cytoplasm. Degranulation of mast cells had occurred and these cells were found in close association with fibroblasts. In some instances phagocytosis of collagen by mast cells was also observed. These observations have led to the hypothesis that transforming growth factor β (TGF-β) derived from mast cells, inhibits keratinocyte proliferation and stimulates increased collagen production through increased expression of lysyl oxidase (LOX) by fibroblasts. Intracellular insoluble collagen formation then occurs due to the rapid, intracellular removal of the C terminal pro-peptide sequence by C-proteinase which initiates the cascade of insoluble collagen fibre formation within the fibroblast. Normally this process occurs only within the ECM in response to the increasing mass of collagen and in an attempt to establish normal tissue homeostasis the mast cells engulf the bundles of collagen fibres. Increased stress on the epidermal layer causes increased keratinocyte proliferation, which results in further growth factor mediated replication of fibroblasts. This creates an endless cycle of collagen synthesis, mast cell degranulation and mast cell mediated collagen phagocytosis, physical stress on the epidermal layer and subsequent growth factor release and fibroblast activation, collagen synthesis and subsequent crowding of keratinocytes and melanocytes. In conclusion, this study identified keloid formation as a defect of procollagen synthesis and processing. Phagocytosis of collagen by mast cells indicates that accumulation of these cells may be a secondary effect to excessive collagen synthesis. In addition, the release of interleukins, mediators and growth factors may further stimulate collagen fibril formation with the imbalance toward increased synthesis. This study also identified and confirmed the findings of other studies that procollagen C-proteinase is an important therapeutic target. Dissertation (MSc)--University of Pretoria, 2014. tm2015 Anatomy MSc Unrestricted 2015-07-02T11:06:00Z 2015-07-02T11:06:00Z 2015/04/24 2014 Dissertation http://hdl.handle.net/2263/45920 Arbi, S 2014, Exploratory descriptive study of the support tissue in keloids, MSc Dissertation, University of Pretoria, Pretoria, viewed yymmdd <http://hdl.handle.net/2263/45920> A2015 29351996 en © 2015 University of Pretoria. All rights reserved. The copyright in this work vests in the University of Pretoria. No part of this work may be reproduced or transmitted in any form or by any means, without the prior written permission of the University of Pretoria. University of Pretoria