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Research of the fimction of SOCS3 in the pathogenesis ofpscriasis using keratinocyte specific SOCS3 knozkout mice

Research of the fimction of SOCS3 in the pathogenesis ofpscriasis using keratinocyte specific SOCS3 knozkout mice
角化细胞特异性SOCS3基因敲除小鼠研究SOCS3在牛皮癣发病机制中的作用
批准号:
18390314
负责人:
HASHIMOTO Koji
金额:
$11.14万
依托单位:
依托单位国家:
日本
项目类别:
Grant-in-Aid for Scientific Research (B)
财政年份:
2006
资助国家:
日本
项目状态:
已结题
起止时间:
2006 至 2007

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中文摘要
翻译
STAT3是一种潜伏的细胞质蛋白,在IL-6、EGF和许多其他生长因子的刺激下向细胞核传递信号。STAT3在细胞增殖、迁移等生物学功能中起着关键作用。细胞因子信号抑制因子(SOCS)调节细胞因子信号的强度。SOCS3受多种细胞因子和其他刺激物的强烈诱导。SOCS3的抑制作用已被证明是相对特定于STAT3的。因此,我们研究了SOCS3在表皮角质形成细胞中的作用。由于SOCS3基因的种系靶向会导致胚胎致死,我们使用Cre/loxP技术结合角蛋白5启动子产生了角化细胞特异性SOCS3缺陷小鼠(KS-SOCS3-/-小鼠)。KS-SOCS3-/-小鼠存活,出生时皮肤外观正常。KS-SOCS3-/-小鼠皮肤未见组织学改变,但20周后皮肤呈红肿鳞片状,部分小鼠耳、尾、背部皮肤出现角化过度病变。皮肤病变的组织学分析显示明显增生,网状嵴伸长,颗粒层丢失和角化不全。这些表型和组织学显示与人类牛皮癣病变有很强的相似性。接下来我们使用胶带剥离,这是一种轻微的表皮损伤。KS-SOCS3-/-小鼠早在剥离后4天就出现鳞状病变,而野生型小鼠表现为轻度表型。KS-SOCS3-/-小鼠的表型延长至剥离后14天,野生型小鼠无明显临床表型。KS-SOCS3-/-小鼠胶带剥离诱导的病变也表现出人类银屑病的组织学特征。KS-SOCS3-/-小鼠表皮角质形成细胞Ki67高度阳性。与野生型小鼠相比,KS-SOCS3-/-小鼠的STAT3磷酸化染色较强。综上所述,表皮角质形成细胞中STAT3的内源性抑制剂SOCS3的缺失导致了人类牛皮癣的临床表型。少
英文摘要
STAT3 is a latent cytoplasmic protein that conveys signals to the nucleus upon stimulation with IL-6, EGF and many other growth factors. STAT3 plays critical roles in biological function such as cell proliferation, migration and so on. Suppressors of cytokine signaling (SOCS) regulate the strength of cytokine signals. SOCS3 is strongly induced by a variety of cytokines and other stimulators. The suppressive effect of SOCS3 has been shown to be relatively specific to STAT3. Therefore we investigated the role of SOCS3 in epidermal keratinocytes. Since germline targeting of the SOCS3 gene resulted in embryonic lethality, we generated keratinocyte-specific SOCS3-deficient mice (KS-SOCS3-/-mice) using Cre/loxP technology in combination with the keratin 5 promoter. KS-SOCS3-/-mice were viable and their skin appeared normal at birth. No histological alterations were found in skin of KS-SOCS3-/-mice, however, after 20 weeks, their skin was red and scaly, hyperkeratotic lesions developed in the … More ear, tail and the back skin in some mice. Histological analysis of skin lesions showed a marked hyperplasia, elongation of rete ridge, loss of granular layer and parakeratosis. These phenotype and histology show a strong resemblance to human psoriasis lesions. Next we utilized tape stripping which is a mild form of epidermal injury. KS-SOCS3-/-mice developed scaly lesions as early as 4days after stripping, whereas wild type mice showed a mild phenotype. The phenotype found in KS-SOCS3-/-mice prolonged until 14 days after stripping when wild type mice showed no obvious clinical phenotype. Tape stripping-induced lesions of KS-SOCS3-/-mice also showed histological feature of human psoriasis. Keratinocytes in the epidermis of KS-SOCS3-/-mice were highly positive for Ki67. Phosphorylated STAT3 staining was strong in KS-SOCS3-/-mice compared to wild type mice. In conclusion, loss of SOCS3, an endogenous inhibitor of STAT3, in epidermal keratinocytes leads to clinical phenotype of human psoriasis. Less
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TAK I is essential for differentiation and the prevention of apoptosis in epidermis
TAK I 对于表皮分化和预防细胞凋亡至关重要
DOI: --
发表时间: 2006
期刊: J Biol Chem 281
影响因子: --
作者: [Sayama, K, Hanakawa, Y, Nagai, H, Shiralcata, Y, Dai, X, Hirakawa, S, Tokumaru, S, Tohyama, M, Yang, L, Sato, S, Shizuo, A, Hashimoto, K]
通讯作者: K
PPARγ/C/EBPalpha signaling pathway plays a key role in 1,25-dihydroxyvitamin D3-induced keratinocyte differentiation.
PPARγ/C/EBPα信号通路在1,25-二羟基维生素D3诱导的角质形成细胞分化中发挥关键作用。
DOI: --
发表时间: 2006
期刊:
影响因子: --
作者: [Y Shirakata, X Dai, S Tokumaru, Y Hanakawa, M Tohyama, L Yang, K Sayama, and K Hashimoto]
通讯作者: and K Hashimoto
PPARgamma is an important transcription factor in lalpha,25-dihyclroxyvitamin 03-induced involucrin expression
PPARgamma 是 lalpha,25-二羟维生素 03 诱导的外皮蛋白表达中的重要转录因子
DOI: --
发表时间: 2008
期刊: I Dermatol Sci 50
影响因子: --
作者: [Dai, X, Sayama, IC, Shirakata, Y, Tokunaru, S, Yang, L, Tohyama, M, Hirakawa, S, Hanakawa, Y, Hashimoto, K]
通讯作者: K
A new skin equivalent using de-epithelialized amnion membrane
使用去上皮羊膜的新皮肤等同物
DOI: --
发表时间: 2007
期刊:
影响因子: --
作者: [Shirakata Y, Yang L, Hashimoto K]
通讯作者: Hashimoto K
共 41 条
    Development of cerebral infarction regenerative treatment by neural stem cell transplant targeting microRNA
    • 批准号:
      16K10715
    • 项目类别:
      Grant-in-Aid for Scientific Research (C)
    • 资助金额:
      $3.0万
    • 财政年份:
      2016
    • 负责人:
      HASHIMOTO Koji
    • 依托单位:
    The role of a novel platelet activated receptor CLEC-2 in the carotid plaque
    • 批准号:
      25861265
    • 项目类别:
      Grant-in-Aid for Young Scientists (B)
    • 资助金额:
      $2.5万
    • 财政年份:
      2013
    • 负责人:
      HASHIMOTO Koji
    • 依托单位:
    Construction of new description of atomic nuclei using superstring theory
    Application of superstring theory to nuclear and quark physics
    海外基金