title: ABCG2 deficiency in skin impairs re-epithelialization in cutaneous wound healing.
abstract: The ATP-binding cassette transporter ABCG2 is expressed in the interfollicular epidermis and mediates the side-population phenotype in skin cells. However, the role of ABCG2 in skin is unclear. Increased expression levels of ABCG2 were found at the basal layer of transitional epidermis adjacent to cutaneous wounds in human patients, indicating that ABCG2 may be involved in regulating the wound healing process. To investigate the role of ABCG2 in cutaneous wound healing, full-thickness skin wounds were created in ABCG2 knockout (ABCG2-KO) and wild-type mice. The healing process was analysed and revealed that ABCG2 deficiency in skin results in delays in wound closure and impairments in re-epithelialization, as evidenced by reductions in both suprabasal differentiation and in p63-expressing keratinocytes migrating from transitional epidermis to epithelial tongues. The reduction in p63-expressing cells may be due to elevated levels of reactive oxygen species in ABCG2-KO epidermis, which can cause DNA damage and lead to proliferation arrest. To determine whether ABCG2 deficiency affects the potency of epidermal stem/progenitor cells (EPCs), transplantation studies were carried out, which demonstrated that ABCG2-KO EPCs display higher levels of γH2AX and lose the capacity to differentiate into suprabasal keratinocytes. A competitive repopulation assay confirmed that ABCG2 expression is critical for the proper expansion and differentiation of EPCs in cutaneous wounds. As EPCs are known to contribute to the healing of larger wounds, the current findings imply a functional role for ABCG2 in the expansion and differentiation of p63-expressing EPCs. Thus, ABCG2 deficiency in skin impairs re-epithelialization in cutaneous wound healing.
authors.affiliation: Institute of Microbiology and Immunology, National Yang-Ming University, Taipei, Taiwan.|Genomics Research Center, Academia Sinica, Taipei, Taiwan.
authors.forename: Hsiao-Min
authors.initials: HM
authors.lastname: Chang
authors.affiliation: Institute of Biomedical Engineering, National Taiwan University, Taipei, Taiwan.
authors.forename: Wen-Yen
authors.initials: WY
authors.lastname: Huang
authors.affiliation: Institute of Biomedical Engineering, National Taiwan University, Taipei, Taiwan.|Department of Dermatology, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan.
authors.forename: Sung-Jan
authors.initials: SJ
authors.lastname: Lin
authors.affiliation: Department of Plastic and Reconstructive Surgery, Buddhist Tzu Chi General Hospital, New Taipei City, Taiwan.
authors.forename: Wei-Chao
authors.initials: WC
authors.lastname: Huang
authors.affiliation: Department of Medical Biotechnology and Laboratory Science, Chang Gung University, Tao-Yuan, Taiwan.
authors.forename: Chia-Rui
authors.initials: CR
authors.lastname: Shen
authors.affiliation: Department of Biotechnology and Laboratory Science in Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Wan-Yu
authors.initials: WY
authors.lastname: Mao
authors.affiliation: Institute of Microbiology and Immunology, National Yang-Ming University, Taipei, Taiwan.|Genomics Research Center, Academia Sinica, Taipei, Taiwan.|Department of Biotechnology and Laboratory Science in Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Chia-Ning
authors.identifier: 0000-0002-0747-217X
authors.initials: CN
authors.lastname: Shen
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2 / Q000172:deficiency* / Q000378:metabolism*; D000328:Adult; D053687:Adult Stem Cells / Q000502:physiology*; D000818:Animals; D004249:DNA Damage; D000078404:Epidermal Cells; D004817:Epidermis / Q000502:physiology*; D005260:Female; D006801:Humans; D008297:Male; D018345:Mice, Knockout; D009363:Neoplasm Proteins / Q000378:metabolism*; D062326:Re-Epithelialization; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; C501412:Abcg2 protein, mouse; D009363:Neoplasm Proteins; D017382:Reactive Oxygen Species
keywords: ABCG2; cutaneous wound healing; epidermal stem cells; re-epithelialization; side population