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

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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.