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Publication : Pituitary tumor transforming gene 1 induces tumor necrosis factor-α production from keratinocytes: implication for involvement in the pathophysiology of psoriasis.

First Author  Ishitsuka Y Year  2013
Journal  J Invest Dermatol Volume  133
Issue  11 Pages  2566-2575
PubMed ID  23677169 Mgi Jnum  J:202058
Mgi Id  MGI:5516549 Doi  10.1038/jid.2013.189
Citation  Ishitsuka Y, et al. (2013) Pituitary Tumor Transforming Gene 1 Induces Tumor Necrosis Factor-alpha Production from Keratinocytes: Implication for Involvement in the Pathophysiology of Psoriasis. J Invest Dermatol 133(11):2566-75
abstractText  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-alpha (TNF-alpha), 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-alpha, and TNF-alpha 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-alpha.
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