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

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。紧致皮肤（TSK/+）小鼠是一种假定的小鼠SSc模型，其特征是皮肤中胶原沉积过多。博来霉素皮下治疗建立了博来霉素诱导的另一种SSc模型小鼠。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通过降低TSK小鼠皮下厚度，显著减少TSK小鼠皮肤纤维化的发生。此外，TSA显著降低了皮肤I型胶原和纤维原性细胞因子的mRNA表达。然而，TSA对博莱霉素诱导的SSc模型皮肤硬化没有减轻作用。这些结果表明，TSA仅通过调节胶原蛋白和纤维化细胞因子的表达来减少TSK小鼠的皮肤纤维化，而不影响全身免疫水平。TSA治疗皮肤硬化的效果可能取决于硬化的发病机制。

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.