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

角化细胞被膜的形成是按顺序发生的，最初涉及到总环蛋白的沉积，随后涉及到SPRR，然后是氯氰菊酯的掺入。银屑病表皮缺乏适当的角化细胞被膜成熟(石田-山本，Iizuka等人；JInvest皮肤醇104：391-395,1995；石田-山本，Iizuka等人；J组织化学细胞化学44：167-175,1996，石田-山本，Iizuka等人；J Invest皮肤醇108：12-16,1997)。典型的银屑病表皮以缺乏角质形成蛋白颗粒为特征，角质形成蛋白的主要成分是Profilaggrin。在去核角质层形成之前，Profilaggrin N-末端结构域被从微丝蛋白重复序列中切割出来，并短暂地定位于凋亡的核(Ishida-Yamamoto，Iizuka；Lab Invest 78：1245-1253,1998)。银屑病表皮的特征是β2-肾上腺素能反应和三氯氯丙烷降低。β2-肾上腺素能受体…基因的表达水平银屑病皮损表皮中的氯丙酸含量较非银屑病皮损的显著降低。与之相反，受累表皮中总蛋白的表达显著增加。这些结果表明，银屑病皮损表皮中β2肾上腺素能受体氯化蛋白和总蛋白的表达变化与不同数量的mRNA转录本有关(Takahashi，Iizuka et al；BR J Dermatol 134：1065-1069,1996)。在角质形成细胞中的各种蛋白激酶C同工酶中，α和et型蛋白激酶C亚型促进了人总蛋白基因的转录。(Takahashi，Iizuka等；J Invest Dennatol 110：218-223,1998)。角蛋白被证明与半胱氨酸蛋白酶抑制剂半胱氨酸蛋白酶抑制剂A相同，并且它在银屑病患者皮损中的表达增加。人类半胱氨酸抑素A基因的5‘侧翼区域被证明具有启动子活性，并且包含一个tre，介导该基因在TPA(Takahashi，Iizuka等人；J Invest Dermatol 108：843-847,1997；Takahashi，Iizuka等人；J Biol Chem273：17375-17380,1998)的增强表达

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