Abstract
Keloid disease (KD) is a fibroproliferative disorder of unknown aetiopatho- genesis with ill-defined treatment. There is increasing evidence to suggest that an aberrant Notch signalling may contribute directly to skin pathogenesis.1–5 Therefore, the aim of this study was to investigate the Notch signalling pathway in KD compared to normal skin obtained from the same patients. Understand- ing the role of Notch signalling involved in cell fate decision in KD may lead to application of new therapies for the treatment of KD. In the present study, we employed in vivo and in vitro novel primary cell culture models to elucidate the role of Notch signalling in 26 Keloid tissue samples, normal skin tissue samples and primary fibroblast cell lines established from the same patients, age ranging from 20–74. We show the presence of a significant (p o 0.05) up-regulation of Notch receptors and ligand JAG-1 in KD compared to normal skin from Keloid patients. Cell spreading, attachment and cell proliferation were signifi- cantly (p o 0.05) reduced in JAG-1 antisense-treated primary fibroblasts iso- lated from KD and treated with gamma-secretase inhibitor, which blocks proteolytic cleavage and activation of Notch, using a novel real time cell ana- lyzer (RTCA) on a microelectronic sensory array. In contrast normal skin fi- broblast cells, isolated from the keloid patients, treated with JAG-1 human recombinant peptide showed significantly (p o 0.05) enhanced cell spreading, attachment and cell proliferation in RTCA in a dose dependent manner. Acti- vation or inhibition of JAG-1 and Notch significantly (p o 0.05) altered the behaviour of primary fibroblasts, isolated from Keloid patients, in cell migra- tion (scratch wound assay), angiogenesis (in vitro co-culture tube formation assay) and cell invasion (novel 3D invasion assay). In conclusion, this is the first study to demonstrate the role of Notch signalling pathway in KD progression and that targeting this pathway might provide a novel strategy for treatment of KD
| Original language | English |
|---|---|
| Title of host publication | host publication |
| Pages | 117-285 |
| Number of pages | 169 |
| Publication status | Published - Apr 2011 |
| Event | 21st Annual Meeting of the Wound Healing Society with SAWC 2011, Dallas, Texas, USA, At Wound Repair and Regeneration - Dallas, Texas, USA Duration: 1 Jan 1824 → … |
Conference
| Conference | 21st Annual Meeting of the Wound Healing Society with SAWC 2011, Dallas, Texas, USA, At Wound Repair and Regeneration |
|---|---|
| City | Dallas, Texas, USA |
| Period | 1/01/24 → … |
