Scar tissue probed

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  • Published: Apr 1, 2010
  • Author: Steve Down
  • Channels: Proteomics
thumbnail image: Scar tissue probed

When we cut or scrape ourselves, scarring is a normal part of the repair process. Connective tissue cells, known as fibroblasts, are deposited in the skin to form gristly fibres which hold the wound closed. In time, the scar will heal up completely to become invisible, or to leave a slight blemish at worst.

However, in a small number of people, the fibroblasts continue to multiply, even when the wound has been filled in. They are forced above the surface of the skin to form smooth mounds of scar tissue which can cover wide areas of the skin.

These phenomena are known as keloid scars and they are more common in darkly pigmented people such as Africans, Afro-Americans and Asian Indians. They can appear following many types of injury, including acne, cuts and scrapes.

Although these are benign growths, they can be extremely unsightly and very itchy. They do not respond well to current treatment regimes. A more complete knowledge of the molecular mechanisms involved in keloid formation might lead to better forms of treatment.

Currently, the causes of keloids have been attributed to the abnormal activity of growth factors or changes in the levels of the components of the extracellular matrix such as collagen or fibronectin. In practice, a combination of these factors plus other, as yet undefined, components might be responsible.

In a move to identify the molecular causes responsible for keloids, a team of scientists from the National University of Sinagpore has undertaken a comparison of the proteomes of normal skin and keloid scars. Senior reporter Thang Phan and colleagues analysed 10 samples of keloid scar tissue from Chinese, Malaysian and Indian subjects and compared them with 10 samples of normal skin from Chinese, Malaysian, Indian and Caucasian subjects.

Protein extracts from each sample were subjected to two-dimensional gel electrophoresis followed by silver staining and image analysis. Normal and keloid skin yielded 598 and 902 proteins, respectively, and those that were differentially expressed were selected for further analysis. Of the 35 and 44 proteins from normal and keloid skin, most were only expressed in their own tissue type, suggesting that each tissue type has its distinct microenvironment.

The selected proteins were identified by the standard protocol of in-gel digestion with trypsin followed by MALDI tandem mass spectrometric analysis of the resultant peptides and database searching. The protein spots corresponded to 23 and 32 proteins when the different isoforms and post-translationally modified forms were taken into account.

Normal skin contained high levels of heat shock proteins, carbonic anhydrase, gelsolin, alpha1-antitrypsin and keratin 1 and 10. On the other hand, keloid skin contained proteins that were either absent from normal skin or up-regulated. Some of the notable differences were discussed by Phan.

The antifibrotic protein asporin functions as a suppressor of transforming growth factor (TGF)-beta1 activity and is generally expressed during the inflammatory response in skin wounds to suppress excessive scar formation. Its high expression in keloid tissue might be a major neutralizing factor to the over-expression of profibrotic TGF-beta1. The researchers will be studying its expression profile along the wound healing course leading to keloid formation in a future study.

The growth suppressor proteins galectin-1 and stratifin were also over-expressed in keloid tissue. They restrict scar formation towards the end of wound healing. A fourth up-regulated protein was macrophage migratory inhibitory factor (MIF), which helps to overcome excessive inflammation and increases formation of collagen and matrix-associated proteins.

This is the first reported proteomic comparison between normal and keloid skin and it has provided several potential therapeutic targets for treatment of keloid scars. However, more work is required to study their expression during the different stages of wound healing before they can be fully evaluated.

The views represented in this article are solely those of the author and do not necessarily represent those of John Wiley and Sons, Ltd.




A keloid scar
Image: Uniformed Services University of the Health Sciences

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