I. S. Haslam1, A. Shahmalak2, R. Paus1, 3
1. Institute of Inflammation and Repair, University of Manchester, Manchester, United Kingdom.
2. Crown Cosma Clinic, Manchester, United Kingdom.
3. Department of Dermatology, University of Luebeck, Luebeck, Germany.
ATP-binding cassette (ABC) transporters fulfil a crucial role in xenobiotic defence across a range of species and tissues. Past research has identified their prominent role in reducing the accumulation of toxins within cells. Certain members of this superfamily, including ABCB1 (P-glycoprotein) and ABCG2 (Breast cancer resistance protein; BCRP) are also expressed in various stem cell populations, conferring the side-population phenotype by exclusion of the dye, Hoechst 33342 (H33342). Currently, expression and function of these membrane transporters in the human hair follicle are unknown. We utilised ABC transporter TaqMan arrays to characterise the expression of their RNA in isolated human hair follicles from 2 male patients. Protein expression and localisation of stem-cell associated and xenobiotic defence ABC transporters (ABCB1, ABCG2, ABCC4 and ABCB5) was examined by immunofluorescent staining. Strong immunoreactivity for ABCB1 was noted in the proximal IRS and terminally differentiating keratinocytes of the bulb. ABCC4 immunofluorescence was particularly prominent throughout the ORS and IRS of the proximal HF, yet absent in the stem-cell-containing bulge. Instead, ABCG2 protein was predominantly expressed in matrix keratinocytes and the bulge region and co-localised with the HF stem cell marker keratin 15. ABCB5 expression was restricted to the ORS of the lower hair follicle. Functional ABCG2 efflux activity was assessed intra-vitally via 30 minutes incubation with the ABCG2 substrate H33342, in the presence and absence of the specific ABCG2 inhibitor Ko143. Application of the inhibitor increased dye accumulation in the bulge region. These data provide the first evidence for expression and functionality of multiple ABC transporters within defined compartments of human hair follicle epithelium, including the stem cell region. ABCG2 may contribute to the protection of stem cells against toxic insult such as chemotherapy.
→ Back to Research