title: Pituitary tumor transforming gene 1 induces tumor necrosis factor-α production from keratinocytes: implication for involvement in the pathophysiology of psoriasis.
abstract: Proliferation and differentiation in the epidermis must be tightly regulated. This regulation is known to involve a range of transcription factors, including pituitary tumor transforming gene 1 (PTTG1), a ubiquitously distributed transcription factor that regulates keratinocyte proliferation and differentiation. Psoriasis is a common but refractory skin disorder, the pathophysiology of which is characterized by hyperproliferation and impaired differentiation in the epidermis. The present study was conducted to clarify the less well-known roles of PTTG1 in the pathophysiology of psoriasis, focusing on its relationship with tumor necrosis factor-α (TNF-α), which is a critical mediator of the disease. The levels of PTTG1 expression were increased in the psoriatic epidermis. Overexpression of PTTG1 resulted in the overproduction of TNF-α, and TNF-α itself had an inductive effect on PTTG1 expression, suggesting that their expression may involve autoinduction. Moreover, overexpression of PTTG1 involved augmented the expression of cyclin A and B1 proteins in both cultured keratinocytes and the psoriatic epidermis. Therefore, enhanced expression of PTTG1 in the psoriatic epidermis may result in aberrant regulation of the cell cycle and impaired differentiation via the interplay between PTTG1 and TNF-α.
authors.affiliation: Department of Dermatology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Ishitsuka
authors.affiliation: Department of Dermatology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan. Electronic address: kyasuhir@md.tsukuba.ac.jp.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Kawachi
authors.affiliation: Department of Dermatology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Maruyama
authors.affiliation: Department of Dermatology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
authors.forename: Shijima
authors.initials: S
authors.lastname: Taguchi
authors.affiliation: Department of Dermatology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Fujisawa
authors.affiliation: Department of Dermatology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
authors.forename: Junichi
authors.initials: J
authors.lastname: Furuta
authors.affiliation: Department of Dermatology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Nakamura
authors.affiliation: Department of Dermatology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Ishii
authors.affiliation: Department of Dermatology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
authors.forename: Fujio
authors.initials: F
authors.lastname: Otsuka
mesh_terms: D000328:Adult; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation; D002478:Cells, Cultured; D019925:Cyclin A / Q000378:metabolism; D056744:Cyclin B1 / Q000378:metabolism; D000078404:Epidermal Cells; D004817:Epidermis / Q000378:metabolism / Q000473:pathology; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D007231:Infant, Newborn; D015603:Keratinocytes / Q000166:cytology / Q000502:physiology*; D011565:Psoriasis / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D064249:Securin / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: C534699:CCNB1 protein, human; D019925:Cyclin A; D056744:Cyclin B1; D064249:Securin; D014409:Tumor Necrosis Factor-alpha; C578002:pituitary tumor-transforming protein 1, human; C512478:EGFR protein, human; D066246:ErbB Receptors