P30 CYCLOSPORIN A STIMULATES HAIR SHAFT PRODUCTION, FOLLICLE KERATINOCYTE PROLIFERATION AS WELL AS HGF AND VEGF EXPRESSION, AND INHIBITS CATAGEN DEVELOPMENT IN ORGAN-CULTURED MOUSE VIBRISSAE FOLLICLES

^1,2Fan WX, ¹Zhu WY,  ²Mecklenburg L, ²Paus R Dermatology Depts, ¹First Affiliated Hospital of Nanjing Medical University, P. R. China; ²Univ Hosp Eppendorf, Univ of Hamburg, Germany

One of the most common side effects of systemic cyclosporin A (CsA) therapy is hypertrichosis. While we have previously shown that CsA stimulates anagen and inhibits catagen development in mice, the underlying mechanisms of action are as yet unknown. Here, we explored the use of a mouse vibrissae model for dissecting these mechanisms by studying the effects of CsA on hair shaft elongation, follicle cell proliferation, and mRNA expression of selected growth factors in organ-culture. Mouse vibrissae follicles in early anagen VI were cultured in William’s E medium with CsA (or vehicle control) for 10 days. Hair shaft elongation, morphological changes in the hair bulb, and follicular ³H-TdR incorporation were assessed. By RT-PCR, HGF and VEGF mRNA expression was measured. Mouse vibrissae follicles treated with 0.01mM CsA produced fine growing fibers with an average growth that exceeded 2.5 mm after 10 days of culture, which was significantly longer than the hair shaft elongation seen in control follicles (P<0.05). This corresponds well to the reported prolongation of human hair follicle in vitro by CsA (JID100: 237). The hair growth-stimulating effect of CsA was concentration-dependent. 0.01-0.1mM CsA also significantly stimulated ³H-TdR incorporation into the hair bulb, while hair growth was significantly suppressed by 1mM CsA. At day 8 of culture, most follicles cultured with CsA displayed an anagen VI-like hair bulb, while control follicles exhibited a morphology reminiscent of catagen development. Interestingly, at day 4 and /or 6 the steady-state levels of HGF and VEGF transcripts were significantly higher in CsA-treated mouse vibrissae follicles than in vehicle-treated controls. These studies show that organ culture of mouse vibrissae follicles offers an attractive model for dissecting the hair growth-modulating effects of CsA and demonstrate that, contrary to a previous study (Lab Invest 62:104), CsA dose stimulate hair growth of normal mouse vibrissae follicles in vitro, possibly in part by enhancing HGF and VEGF expression.