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

11 Citations (Scopus)

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.

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

Fingerprint

ATP-Binding Cassette Transporters
Hair Follicle
Fluorescence Microscopy
Stem Cells
Hypertrichosis
Physiological Phenomena
Lipids
Polymerase Chain Reaction
Active Biological Transport
Alopecia
Multiple Drug Resistance
Xenobiotics
Scalp
Prostaglandins
Cell Movement
Cell Differentiation
Coloring Agents
Epithelium
Adenosine Triphosphate
Epithelial Cells

Cite this

Haslam, I. S. ; El-Chami, C. ; Faruqi, H. ; Shahmalak, A. ; O'Neill, C. A. ; Paus, R. / Differential expression and functionality of ATP-binding cassette transporters in the human hair follicle. In: British Journal of Dermatology. 2015 ; Vol. 172, No. 6. pp. 1562-1572.
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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.",
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Differential expression and functionality of ATP-binding cassette transporters in the human hair follicle. / Haslam, I. S.; El-Chami, C.; Faruqi, H.; Shahmalak, A.; O'Neill, C. A.; Paus, R.

In: British Journal of Dermatology, Vol. 172, No. 6, 06.2015, p. 1562-1572.

Research output: Contribution to journalArticle

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T1 - Differential expression and functionality of ATP-binding cassette transporters in the human hair follicle

AU - Haslam, I. S.

AU - El-Chami, C.

AU - Faruqi, H.

AU - Shahmalak, A.

AU - O'Neill, C. A.

AU - Paus, R.

N1 - No full text in Eprints. HN 14/11/2017

PY - 2015/6

Y1 - 2015/6

N2 - 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.

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SN - 0007-0963

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