title: A transcriptional roadmap to the senescence and differentiation of human oral keratinocytes.
abstract: Human epithelial cells undergo morphological and molecular changes leading to terminal differentiation and replicative senescence after a finite number of cell divisions during serial subculture. However, the target genes and their functional significance in the senescence and differentiation in normal human oral keratinocytes have been poorly defined. Here, we demonstrated normal human oral keratinocytes transcriptional signature profiling to senescence and differentiation. Using microarray analysis, our findings indicated that the gene expression profiles induced by serial subculture are distinct classes of gene. The greatest number of these altered genes was identified as being related to biological pathways of transport, cell proliferation, cell cycle, defense and immune response, cell death, transcription, apoptosis, and inflammatory response, suggesting that the serial subculture is able to induce a multitude of specific gene expression changes during senescence and differentiation. Several highly upregulated genes (IL-1β, S100A8, S100A9, MMP1, MMP9, IL-8, BHLHB2, HES1, and TWIST1) in response to the serial subculture in normal human oral keratinocytes were observed. In vitro and in vivo studies also exhibited a close relationship between senescence and differentiation of primary oral keratinocytes and expression of inflammatory molecules. These results suggest a new approach to determine the biological events underlying the pathogenesis of oral keratinocyte aging.
authors.affiliation: Department of Oral Biochemistry and Program in Cancer and Developmental Biology, Dental Research Institute, Seoul National University, School of Dentistry, Seoul, Korea.
authors.forename: Da Hyun
authors.initials: DH
authors.lastname: Jang
authors.affiliation: Department of Biochemistry and Molecular Biology, Nihon University School of Dentistry at Matsudo, Chiba, Japan.
authors.forename: Ujjal K
authors.initials: UK
authors.lastname: Bhawal
authors.affiliation: Department of Internal Medicine, The Catholic University of Korea, Seoul.
authors.forename: Hong-Ki
authors.initials: HK
authors.lastname: Min
authors.affiliation: Department of Oral Biochemistry and Program in Cancer and Developmental Biology, Dental Research Institute, Seoul National University, School of Dentistry, Seoul, Korea.
authors.forename: Hyun Ki
authors.initials: HK
authors.lastname: Kang
authors.affiliation: Department of Biochemistry and Molecular Biology, Nihon University School of Dentistry at Matsudo, Chiba, Japan.
authors.forename: Yoshimitsu
authors.initials: Y
authors.lastname: Abiko
authors.affiliation: Department of Oral Biochemistry and Program in Cancer and Developmental Biology, Dental Research Institute, Seoul National University, School of Dentistry, Seoul, Korea. bmmin@snu.ac.kr.
authors.forename: Byung-Moo
authors.initials: BM
authors.lastname: Min
mesh_terms: D000375:Aging / Q000235:genetics; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics*; D049109:Cell Proliferation / Q000235:genetics; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000187:drug effects / Q000235:genetics*; D053263:Gene Regulatory Networks; D019942:Genes, p16; D005881:Gingiva / Q000166:cytology; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D053583:Interleukin-1beta / Q000235:genetics / Q000494:pharmacology; D015603:Keratinocytes / Q000166:cytology* / Q000378:metabolism*; D051379:Mice; D011498:Protein Precursors / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D018398:Homeodomain Proteins; D053583:Interleukin-1beta; D011498:Protein Precursors; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; C491539:Bhlhe40 protein, mouse; C467480:vascular endothelial growth factor A, mouse; C032253:involucrin
keywords: Human oral keratinocytes; cell differentiation; gene network.; replicative senescence