The effect of trichostatin A, one of the histone deacetylaseinhibitor, on skin fibrosis of systemic sclerosis mouse model

组蛋白脱乙酰酶抑制剂之一曲古抑菌素A对系统性硬化症小鼠模型皮肤纤维化的影响

• 批准号: 22591245
• 负责人: OGAWA Fumihide
• 金额: $ 2.83万
• 依托单位: Nagasaki University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2010
• 资助国家: 日本
• 起止时间: 2010 至 2012
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-22591245/
• 关键词: 強皮症; 膚硬化; ストン脱アセチル化酵素; モデルマウス; トリコスタチンA; 皮膚硬化; ヒストン脱アセチル化酵素; トリコスタチンＡ; ピストン脱アセチル化酵素

Systemic sclerosis (SSc) is connective tissue disorder characterized by severe fibrosis of the skin and various internal organs. Tight skin (TSK/+) mouse is a putative murine model of SSc characterized by excessive collagen deposition in skin. Bleomycin-induced SSc model mouse, which is another model of SSc, is established using subcutaneous bleomycin treatment. TSA was injected subcutaneously into the back of the TSK/+, bleomycin-induced SSc model mice, and wild type mice. TSA significantly decreased the development of TSK mouse skin fibrosis by reducing the hypodermal thickness. Furthermore, skin mRNA expressions of type I collagen and fibrogenic cytokines were markedly attenuated by TSA administration. However, TSA could not decrease the skin sclerosis of bleomycin-induced SSc model. These results suggest that TSA decreases skin fibrosis only in TSK mouse by regulating expression of collagen and fibrogenic cytokines and does not affect systemic immune level. The effect of TSA for skin sclerosis may depend on the pathogenesis of sclerosis.

系统性硬化症（SSc）是一种结缔组织疾病，其特征是皮肤和各种内脏器官的严重纤维化。紧皮肤（TSK/+）小鼠是推定的 SSc 小鼠模型，其特征是皮肤中胶原蛋白沉积过多。博来霉素诱导的SSc模型小鼠是另一种SSc模型，是通过皮下注射博来霉素治疗建立的。将 TSA 皮下注射到 TSK/+、博莱霉素诱导的 SSc 模型小鼠和野生型小鼠的背部。 TSA 通过减少皮下组织厚度显着减少 TSK 小鼠皮肤纤维化的发展。此外，施用 TSA 后，皮肤 I 型胶原蛋白和纤维细胞因子的 mRNA 表达显着减弱。然而，TSA不能减少博来霉素诱导的SSc模型的皮肤硬化。这些结果表明，TSA 仅通过调节胶原蛋白和纤维形成细胞因子的表达来减少 TSK 小鼠的皮肤纤维化，并且不影响全身免疫水平。 TSA 对皮肤硬化的作用可能取决于硬化的发病机制。

项目成果

Autoantibodies to small ubiquitin-like modifier activating enzymes in Japanese patients with dermatomyositis: comparison with a UK Caucasian cohort.

日本皮肌炎患者的小泛素样修饰剂激活酶自身抗体：与英国白种人队列的比较。

• DOI: 10.1136/annrheumdis-2012-201736
• 发表时间: 2013
• 影响因子: 27.4
• 作者: Fujimoto M

Autoantibodies to small ubiquitin-like modifier activating enzymes in Japanese patients with dermatomyositis: comparison with a UK Caucasian cohort

日本皮肌炎患者的小泛素样修饰剂激活酶自身抗体：与英国白种人队列的比较

• 发表时间: 2013
• 影响因子: 27.4
• 作者: Fujimoto M; Matsushita T; Hamaguchi Y; Kaji K; Asano Y; Ogawa F; Yamaoka T; Fujikawa K; Tsukada T; Sato K; Echigo T; Hasegawa M; Takehara K
• 通讯作者: Takehara K

Periorbital milia-like calcinosis

眶周粟粒样钙质沉着症

• 发表时间: 2012
• 影响因子: 4.1
• 作者: Tomita H; Ogawa F; Yoshizaki A; Akiyama Y; Kinoshita N; Utani A
• 通讯作者: Utani A

Periorbital milia-like calcinosis.

眶周粟丘疹样钙质沉着。

• DOI: 10.1111/j.1365-2230.2012.04348.x
• 发表时间: 2012
• 影响因子: 4.1
• 作者: Tomita H