Pigmentation Diathesis of Hypertrophic Scar: An Examination of Known Signaling Pathways to Elucidate the Molecular Pathophysiology of Injury-Related Dyschromia.

Available online through MWHC library: 2006 - present, Available in print through MWHC library: 2006 - present

Hypertrophic scar (HTS) occurs frequently after burn injury. Treatments for some aspects of scar morbidity exist, however, dyspigmentation treatments are lacking due to limited knowledge about why scars display dyschromic phenotypes. Full thickness wounds were created on duroc pigs that healed to form dyschromic HTS. HTS biopsies and primary cell cultures were then used to study pigmentation signaling. Biopsies of areas of both pigment types were taken for analysis. At the end of the experiment, melanocyte-keratinocyte co-cultures were established from areas of differential pigmentation. Heterogeneously dyspigmented scars formed with regions of hyperpigmentation and hypopigmentation. Melanocytes were present in both pigment types measured by S100beta qRT-PCR and immunostaining, and visualized by dendritic cell presence in primary cultures. P53 expression was not different between the two pigment types. Hyperpigmented scars had up regulated levels of POMC, ACTH, alpha-MSH, SCF, and c-KIT and MC1R receptors compared to hypopigmented regions. Many genes involved in dyspigmentation were differentially regulated by microarray analysis including MITF, TYR, TYRP1, and DCT. MiTF expression was not different upon further exploration, but TYR, TYRP1, and DCT were up regulated in intact biopsies measured by qRT-PCR and confirmed by immunostaining. This is the first work to confirm the presence of melanocytes in hypopigmented scar using qRT-PCR and primary cell culture. An understanding of the initial steps in dyspigmentation signaling, as well as the downstream effects of these signals, will inform treatment options for patients with scars and provide insight to where pharmacotherapy may be directed.

English