Hypertrophic Scar And The Cutaneous HPA Axis

Objective:The expression of the "cutaneous HPA axis" in the skin functions as an important component of the local response to cutaneous stress. This research is aimed to investigate the relationship between hypertrophic scar and the "cutaneous HPA axis".Methods:1. Quantified the mRNA expressions of corticotrophin-releasing hormone (CRH), CRH receptor 1 (CRH-R1), pro-opiomelanocortin (POMC), melanocortin 2 receptor (MC2R) and gulcocorticoid receptors (GRs) by real-time RT-PCR in hypertrophic scar (n=12) and normal skin tissues (n=7).2. Performed the standard light microscopy immunohistochemistry on paraffin-embedded tissue sections by using the immunoperoxidase staining technique. The antibodies are rabbit anti-CRH; rabbit anti-CRHR1; anti-adrenocorticotropic hormone (ACTH); rabbit anti-MC-2R; mouse anti-GRa.3. Cultured fibroblast from hypertrophic scar and normal skin; incubated CRH or ACTH in three concentrations 10-6M,10-7M and10-8M (added CRH or ACTH into normal skin fibroblast in 10"7M only), for 24h. Collected the media and cells for analysis. Quantified the mRNA expressions of pro-opiomelanocortin (POMC) by real time RT-PCR and measured the productions of ACTH and gulcocorticoids by ELISA.Results:1. The mRNA expressions of CRH, CRH-R1, POMC and GR-a in hypertrophic scar came out to be significantly lower (p<0.05) than in the normal skin, except the MC-2R(P=0.15).2. The immunoperoxidase staining demonstrated the expressions of CRH, CRH-R1, ACTH, MC-2R and GR-a in both hypertrophic scar and normal skin; in where the nuclei of basal epidermal cells and fibroblast cells were highly stained. In addition, sebaceous gland and hair follicular were stained only in normal skin tissues. 3. In hypertrophic scar fibroblast and normal skin fibrolast, POMC gene expression, and ACTH production and secretion responded to CRH stimulation (p<0.05); as well as gulcocorticoids production also reacted to CRH (p<0.05) and ACTH (p<0.05) modulation, and ACTH being more potent.Conclusions:The data of our experiments had been confirmed that the hypertrophic scar could express the components of the HPA axis on both of gene and protein level, but the genetic production in the scar was significantly lower than it was in the normal skin tissue. The experiments found out the HPA axis elements expressed in hypertrophic scar fibroblast could be activated as an regulatory loops similar to the central HPA axis, in vitro. The results implicated that the "cutaneous HPA axis" dysfunction is revelant to the hypertrophic scar formation.