AIM
Despite extensive research into keloid scarring etiopathogenesis, no biomarker has led to an effective therapy. Retinoic acid (RA) has been implicated in key functions including cell cycle regulation, apoptosis, and cell differentiation and shown to affect profibrotic factors, including Transforming growth factor β. However, confirmation of the genetic expression and manipulation of this molecular target have not yet been explored in keloids. The aim, here, was to develop and test new hypotheses underlying keloids by taking the novel approach of examining this entity from both site-specific and dermoepidermal perspectives, leading to targeted potential therapies.
METHODS
Normal skin and keloid biopsies, harvested from the centre and margin of the lesion, were cryosectioned and laser capture microdissected, where the epidermis and dermis were separately collected and microarrayed (whole genome array). Data were analyzed using Array Studio v7.2 and filtered (criteria: p value < 0.05, q value < 0.05, and fold change ≥2). The resultant list of genes was enriched using ingenuity pathway analysis and key pathways identified then validated with qPCR and protein studies (western blot and immunohistochemistry/immunocytochemistry).
RESULTS
The keloid epidermis revealed the reductase enzyme AKR1B10 to be significantly upregulated (p value, 1.19E − 06; fold change, 75). Quantitative real-time polymerase chain reaction confirmed this and dysregulation of other members of the RA pathway. Aldo-keto reductase family 1, member B10 overexpression through transfection of normal keratinocytes changes RA receptor activity and fibrotic gene expression.
CONCLUSIONS
The manipulation of AKR1B10 to ascertain its effect on RA activity and the consequent downstream events in keloid with regard to regulation of fibrosis represents compelling therapeutic potential.
Footnotes
Presented at the Irish Association of Plastic Surgeons Meeting, May 14-15 2015, Galway, Ireland.
Disclosure: The authors have no financial interest to declare in relation to the content of this article. The Article Processing Charge was paid for by The Irish Association of Plastic Surgeons.
IAPS: Irish Association of Plastic Surgeons (IAPS) Summer Meeting, in Galway, Ireland, May 14-15, 2015.