Differential expression and functionality of ATP-binding cassette transporters in the human hair follicle

I. S. Haslam, C. El-Chami, H. Faruqi, A. Shahmalak, C. A. O'Neill, R. Paus

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

Background ATP-binding cassette (ABC) transporters are involved in the active transport of an extremely diverse range of substrates across biological membranes. These transporters are commonly implicated in the development of multidrug resistance and are also involved in numerous physiological and homeostatic processes, including lipid transport, cell migration and differentiation. Objectives To close the knowledge gap in the expression of ABC transporters in the human hair follicle (HF). Methods Quantitative polymerase chain reaction (qPCR) of ABC genes and immunofluorescence microscopy analysis of cryosections of human HFs. Results By qPCR analysis, numerous members of the ABC transporter superfamily, such as ABCB1, ABCG2 and ABCA12, were found to be transcribed in full-length human scalp HFs. Immunofluorescence microscopy demonstrated that the intrafollicular protein expression of different xenobiotic ABC transporters (ABCB1, ABCC1, ABCC4, ABCG2) varies greatly, with ABCG2 expression restricted primarily to the epithelial stem cell region of the outer root sheath (bulge), whereas expression of ABCB1, ABCC1 and ABCC4 was more widespread. Lipid transporters ABCA1, ABCA12 and ABCA4 were almost uniformly expressed throughout the HF epithelium. Functional ABCB1/G2 activity was demonstrated by exclusion of the substrate dye, Hoechst 33342. In the bulge, this was reversed by ABCB1 and ABCG2 inhibition. Conclusions These data encourage further investigation of ABC transporters as potentially important regulators of HF epithelial biology. Clinically, pharmacological modulation of the activity of selected intrafollicular ABC transporters may permit novel therapeutic interventions, such as protecting HF stem cells from chemotherapy-induced damage, counteracting cholesterol-associated hypertrichosis, and manipulating the intrafollicular prostaglandin balance in androgenetic alopecia. What's already known about this topic? ATP-binding cassette (ABC) transporters are expressed in the epidermis and cutaneous immune cells (Langerhans cells). ABCB1 and ABCG2 may enhance the transepidermal movement of substrate drugs. ABCC1 is present in the hair follicle. What does this study add? A detailed expression and localization map for numerous well-characterized xenobiotic and lipid-transporting ABC proteins in the human hair follicle. The first functional data indicating that ABCB1 and ABCG2 actively reduce the accumulation of substrates within the hair follicle.

Original languageEnglish (US)
Pages (from-to)1562-1572
Number of pages11
JournalBritish Journal of Dermatology
Volume172
Issue number6
DOIs
StatePublished - Jun 1 2015
Externally publishedYes

ASJC Scopus subject areas

  • Dermatology

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