|Budget Amount *help
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1989: ¥300,000 (Direct Cost: ¥300,000)
Fiscal Year 1988: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1987: ¥1,000,000 (Direct Cost: ¥1,000,000)
The pathogenesis of psoriasis still remains unknown in spite of numerous studies. We have been studying its biochemical properties, such as cyclic nucleotides, protein kinases, epidermal growth factor, and phospholipases. Through these studies, it has been speculated that altered membrane signal-transduction in involved psoriatic epidermal cells may be one of the main pathomechanisms of psoriasis. In order to investigate further into signal transduction system of psoriasis, we have started the study utilizing molecular biological methods; especially focussing upon oncogenes. Recent advances in molecular biology have defined not only oneogenes are involved in malignant transformation, but also they are essential genes to maintain normal structures and functions in every eukaryotes. It has been clarified that oncogene products have molecular homology to membrane-receptors, transducers, protein kinases, and nucleic binding proteins. In the present project, expressions of oncogenes in prot
ein and mRNA of psoriatic skin were studied for the deeper understanding of the pathogenesis of psoriasis.
<oneogene product> ras gene product designated as ras p21 was immunohistochemically examined with monoclonal anti-ras p2l antibodies in freshly frozen skin tissues obtained from psoriasis involved areas and uninvolved areas of patients and from normal skin of healthy controls. It was obvious that psoriasis involved epidermis expresses more abundantly ras P21 than psoriasis uninvolved and normal epidermis. Enhanced expression of ras P21 is also present in very early psoriatic lesions (pin-point lesion), and disappears when lesions are treated and become clinically normal.
<oncogene in mRNA> poly(A)^+mRNAs were purified from the above skin tissues, and expressions of various oncogenes were analyzed by Northern blot hybridization. H and N-ras expressions had no differences among involved, uninvolved, and normal skin. However, K-ras expression was increased, and one of the transcripts(1.6kb) was lacking in involved skin. Expression of fos, myc, and EGF-receptor gene were rather decreased in involved skin.
Among various oncogenes, increased expression of ras p21 and K-ras mRNA may well be correlated with biochemically characterized change of psoriatic epidermis, that is decreased cAMP responses to some signals. Because ras gene product has a homology to G-protein functioning as a signal transducer, present results suggest that altered K-ras gene may cause abnormal signal-transduction system resulting in the hyperproliferative condition of psoriatic epidermis. To obtain a conclusive evidence whether a lack of one K-ras transcript in psoriasis involved skin may reflect genetic background of psoriasis, further investigations are required. Less