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

Br J Dermatol. 2015 Jun;172(6):1562-1572. doi: 10.1111/bjd.13549. Epub 2015 Mar 19.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter 1 / metabolism
  • ATP Binding Cassette Transporter, Subfamily B / metabolism
  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters / genetics
  • ATP-Binding Cassette Transporters / metabolism
  • ATP-Binding Cassette Transporters / physiology*
  • Benzimidazoles / pharmacology
  • Cells, Cultured
  • Epithelium / metabolism
  • Fluorescent Dyes / pharmacology
  • Hair Follicle / metabolism*
  • Humans
  • Keratinocytes / metabolism
  • Male
  • Multidrug Resistance-Associated Proteins / metabolism
  • Neoplasm Proteins / metabolism
  • RNA, Messenger / metabolism

Substances

  • ABCA1 protein, human
  • ABCA12 protein, human
  • ABCA4 protein, human
  • ABCB1 protein, human
  • ABCC4 protein, human
  • ABCG2 protein, human
  • ATP Binding Cassette Transporter 1
  • ATP Binding Cassette Transporter, Subfamily B
  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters
  • Benzimidazoles
  • Fluorescent Dyes
  • Multidrug Resistance-Associated Proteins
  • Neoplasm Proteins
  • RNA, Messenger
  • bisbenzimide ethoxide trihydrochloride
  • multidrug resistance-associated protein 1