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。皮肤紧绷（TSK/+）小鼠是一种假定的SSc小鼠模型，其特征在于皮肤中过度的胶原沉积。博来霉素诱导的SSc模型小鼠是另一种SSc模型，使用皮下博来霉素治疗建立。将TSA皮下注射到TSK/+、博来霉素诱导的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，显著降低TSK小鼠皮肤纤维化的发展。此外，TSA给药显著减弱了皮肤I型胶原和纤维化细胞因子的mRNA表达。但TSA不能减轻博莱霉素诱导的SSc模型的皮肤硬化。提示TSA仅通过调节胶原和致纤维化细胞因子的表达来减轻TSK小鼠皮肤纤维化，而不影响全身免疫水平。TSA对皮肤硬化的疗效可能与硬化的发病机制有关。

项目成果

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
• 期刊: Clin Exp Dermatol
• 影响因子: 4.1
• 作者: Tomita H;Ogawa F;Yoshizaki A;Akiyama Y;Kinoshita N;Utani A;佐野栄紀;Tomita H
• 通讯作者: Tomita H