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Differential expression and functionality of ATP ‐binding cassette transporters in the human hair follicle
Author(s) -
Haslam I.S.,
ElChami C.,
Faruqi H.,
Shahmalak A.,
O'Neill C.A.,
Paus R.
Publication year - 2015
Publication title -
british journal of dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.304
H-Index - 179
eISSN - 1365-2133
pISSN - 0007-0963
DOI - 10.1111/bjd.13549
Subject(s) - hair follicle , library science , medicine , art history , history , computer science
Summary 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 HF s. Results By qPCR analysis, numerous members of the ABC transporter superfamily, such as ABCB 1, ABCG 2 and ABCA 12, were found to be transcribed in full‐length human scalp HF s. Immunofluorescence microscopy demonstrated that the intrafollicular protein expression of different xenobiotic ABC transporters ( ABCB 1, ABCC 1, ABCC 4, ABCG 2) varies greatly, with ABCG 2 expression restricted primarily to the epithelial stem cell region of the outer root sheath (bulge), whereas expression of ABCB 1, ABCC 1 and ABCC 4 was more widespread. Lipid transporters ABCA 1, ABCA 12 and ABCA 4 were almost uniformly expressed throughout the HF epithelium. Functional ABCB 1/G2 activity was demonstrated by exclusion of the substrate dye, Hoechst 33342. In the bulge, this was reversed by ABCB 1 and ABCG 2 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.