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

银屑病表皮细胞增殖和角化的紊乱调节：紊乱信号系统的分析。

• 批准号: 08457233
• 负责人: IIZUKA Hajime
• 金额: $ 4.54万
• 依托单位: ASAHIKAWA MEDICAL COLLEGE
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08457233/
• 关键词: psoriasis; cornified cell envelope; involucrin; loricrin; filaggrin; protein kinase C; cystatin A; granular layer; ロリクリン; フィラグリン; トランスグルタミナーゼ; 角化; ケラトリニン; 周辺帯

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

皮层细胞被膜的形成是顺序发生的，最初涉及外皮蛋白沉积，随后涉及SPRR，然后涉及兜甲蛋白掺入。银屑病表皮表现出缺乏适当的皮质细胞包膜成熟（Ishida-Yamamoto，Iizuka等; J Invest Dermatol 104：391-395，1995 ; Ishida-Yamamoto，Iizuka等; J Histochem Cytochem 44：167-175，1996，Ishida-Yamamoto，Iizuka等; J Invest Dermatol 108：12-16，1997）。典型的银屑病表皮的特征在于缺乏透明角质蛋白颗粒，其主要成分是前聚丝蛋白。研究表明，丝聚蛋白原N末端结构域从丝聚蛋白重复序列中切割出来，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）。银屑病表皮的特征是β 2-肾上腺素能反应和兜甲蛋白减少。β 2-肾上腺素能受体mRNA水平 ...更多信息 与未受累表皮相比，受累银屑病表皮中的兜甲蛋白显着降低。与此相反，外皮蛋白mRNA表达的参与表皮显着增加。这些结果表明，在银屑病累及的表皮中，β 2-肾上腺素能受体兜甲蛋白和外皮蛋白表达的改变与每种mRNA转录物的不同数量有关（Takahashi，Iizuka等人; 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，蛋白激酶C的α和埃特异构体刺激人外皮蛋白基因的转录。（Takahashi，Iizuka等; J Invest Dennatol 110：218-223，1998）。角蛋白显示与半胱氨酸蛋白酶抑制剂A（一种半胱氨酸蛋白酶抑制剂）相同，并且其表达在银屑病累及的表皮中增加。人半胱氨酸蛋白酶抑制剂A基因的5 ′侧翼区显示出赋予启动子活性，并含有一个TRE，该TRE介导TPA增强该基因的表达（Takahashi，Iizuka等; J Invest Dermatol 108：843- 847，1997; Takahashi，Iizuka等; J Biol Chem 273：17375- 17380，1998）

项目成果

Takahashi H,Asano K,Kinouchi M,Ishida-Yamamoto A,Wuepper KD,Iizuka H: "Structure and transcriptional regulation of human cystatin A gene : The 12-O-tetradecanoyl [phorbol-13-acetate (TPA responsive element-2 site (-272 to -278) on cystatin A gene is criti

Takahashi H、Asano K、Kinouchi M、Ishida-Yamamoto A、Wuepper KD、Iizuka H：“人半胱氨酸蛋白酶抑制剂 A 基因的结构和转录调控：12-O-十四烷酰基 [佛波醇 13-乙酸酯（TPA 响应元件 2 位点）

Takahashi H,Kinouchi M,Tamura T,Ishida-Yamamoto A,Iizuka H: "Adenylate cyclases in keratinocytes : FRSK cells express types I,II,III,IV and VIII,and 1,25 (OH) 2D3, retinoic acid and TPA augment forskolin-induced cyclic AMP accumulation in the adsence of a

Takahashi H、Kinouchi M、Tamura T、Ishida-Yamamoto A、Iizuka H：“角质形成细胞中的腺苷酸环化酶：FRSK 细胞表达 I、II、III、IV 和 VIII 型，以及 1,25 (OH) 2D3、视黄酸和 TPA

Ishida-Yamamoto A, Takahashi H, Presland RB, Dale BA, Iizuka H: "Translocation of profilaggrin N-terminal domain into keratinocyte nuclei with fragmented DNA in normal human skin and loricrin keratoderma" Lab Invest. 78. 1245-1253 (1998)

Ishida-Yamamoto A、Takahashi H、Presland RB、Dale BA、Iizuka H：“丝聚合蛋白原 N 末端结构域易位至正常人皮肤和兜甲蛋白角化病中具有片段 DNA 的角质形成细胞核中”实验室投资。

Takahashi H,Hashimoto Y,Kinouchi M,Iizuka H: "Interferon-gamma-dependent induction of manganese superoxide dismutase activity of SV40-transformed human keratinocytes by anti-Fas antibody and by TNF-alpha" J Dermatol Sci. 16. 191-199 (1998)

Takahashi H、Hashimoto Y、Kinouchi M、Iizuka H：“抗 Fas 抗体和 TNF-α 对 SV40 转化的人角质形成细胞的锰超氧化物歧化酶活性的干扰素γ依赖性诱导”J Dermatol Sci。

Ishida-Yamamoto,Iizuka et al: "Translocation of profilaggrin N-terminal domain into keratinocyte nuclei with fragmented DNA in normal human skin and loricrin keratoderma" Laboratory Investigation. 78. 1245-1253 (1998)

Ishida-Yamamoto、Iizuka 等人：“在正常人皮肤和兜甲蛋白角化病中，聚丝蛋白原 N 末端结构域易位到带有片段 DNA 的角质形成细胞核中”实验室研究。