DISORGANIZED REGULATION OF CELL PROLIFERATION AND KERATINIZATION OF PSORIATIC EPIDERMIS : ANALYSIS OF DERANGED SIGNALING SYSTEM.

角化细胞包膜的形成是顺序发生的，最初涉及到天花苷沉积，随后涉及到SPRR，然后是氯虫苷掺入。银屑病表皮缺乏适当的角化细胞包膜成熟（Ishida-Yamamoto， Iizuka等；J皮肤科杂志104:391-395,1995;Ishida-Yamamoto， Iizuka等；J组织化学细胞化学44:167- 175,1996，Ishida-Yamamoto等；J皮肤科杂志108:12- 16,1997）。典型的银屑病表皮以缺乏角透明素颗粒为特征，其主要成分是侧聚蛋白。聚丝蛋白n端结构域从聚丝蛋白重复序列中断裂，并在去核角质层形成之前短暂定位于凋亡细胞核（Ishida-Yamamoto, Iizuka; Lab Invest 78: 1245-1253,1998）。银屑病表皮的特点是β -肾上腺素能反应和氯克林降低。银屑病受累表皮β 2-肾上腺素能受体和loricrin mRNA水平明显低于未受累表皮。与此相反，受累表皮的involucrin mRNA表达量显著升高。这些结果表明，银屑病相关表皮中β -肾上腺素能受体loricrin和involucrin的表达改变与不同mRNA转录物的数量有关（Takahashi， Iizuka等；Br J Dermatol 134: 1065-1069, 1996）。在角质形成细胞的多种蛋白激酶C同工酶中，蛋白激酶C的α和e同工酶可刺激人天花素基因的转录。（Takahashi, Iizuka et al .; J Invest Dennatol 110: 218-223, 1998）。角化素与半胱氨酸蛋白酶抑制剂胱抑素A相同，其表达在银屑病累及的表皮中增加。人类胱抑素A基因的5'-翼区被证明具有启动子活性，并且含有一个介导TPA增强该基因表达的TRE （Takahashi, Iizuka et al; J Invest Dermatol 108: 843-847,1997; Takahashi, Iizuka et al; J Biol Chem 273: 17375-17380,1998）

Formation of cornified cell envelope was shown to occur sequentially, initially involving involucrin deposition and subsequently involving SPRR and then loricrin incorporation. Psoriatic epidermis demonstrated a lack of proper cornified cell envelope maturation (Ishida-Yamamoto, Iizuka et al ; J Invest Dermatol 104 : 391-395, 1995 ; Ishida-Yamamoto, Iizuka et al ; J Histochem Cytochem 44 : 167-175, 1996, Ishida-Yamamoto, Iizuka et al ; J Invest Dermatol 108 : 12-16, 1997). Typical psoriatic epidermis has been characterized by a lack of keratohyalin granule, the main constituent of which is profilaggrin. The profilaggrin N-terminal domains were shown to be cleaved from the filaggrin repeats and transiently localized to apoptotic nuclei just before the formation of enucleated stratum corneum (Ishida-Yamamoto, Iizuka ; Lab Invest 78 : 1245-1253,1998).Psoriatic epidermis has been characterized by decreased beta2-adrenergic response and loricrin. The mRNA levels of beta2-adrenergic receptor … More and loricrin in the involved psoriatic epidermis was shown to be significantly decreased compared with the uninvolved epidermis. In contrast, involucrin mRNA expression of the involved epidermis was significantly increased. These results indicate that the altered expression of the beta2-adrenergic receptor, loricrin and involucrin, in the psoriatic involved epidermis, is associated with different amounts of each mRNA transcript (Takahashi, Iizuka et al ; Br J Dermatol 134 : 1065-1069, 1996).Among various protein kinase C isozymes in keratinocytes, the alfa and ete isoforms of protein kinase C stimulated transcription of human involucrin gene. (Takahashi, Iizuka et al ; J Invest Dennatol 110 : 218-223, 1998).Keratolinin was shown to be identical with cystatin A, a cysteine proteinase inhibitor, and its expression was increased in the psoriatic involved epidermis. The 5'-flanking region of the human cystatin A gene was shown to confer promoter activity and contains a TRE that mediates the enhanced expression of this gene by TPA (Takahashi, Iizuka et al ; J Invest Dermatol 108 : 843-847,1997 ; Takahashi, Iizuka et al ; J Biol Chem 273 : 17375-17380,1998) Less