HDAC inhibitors in experimental liver and kidney fibrosis.

Katrien Van Beneden, Inge Mannaerts, Marina Pauwels, Christiane Van den Branden, Leo A van Grunsven
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引用次数: 90

Abstract

Histone deacetylase (HDAC) inhibitors have been extensively studied in experimental models of cancer, where their inhibition of deacetylation has been proven to regulate cell survival, proliferation, differentiation and apoptosis. This in turn has led to the use of a variety of HDAC inhibitors in clinical trials. In recent years the applicability of HDAC inhibitors in other areas of disease has been explored, including the treatment of fibrotic disorders. Impaired wound healing involves the continuous deposition and cross-linking of extracellular matrix governed by myofibroblasts leading to diseases such as liver and kidney fibrosis; both diseases have high unmet medical needs which are a burden on health budgets worldwide. We provide an overview of the potential use of HDAC inhibitors against liver and kidney fibrosis using the current understanding of these inhibitors in experimental animal models and in vitro models of fibrosis.

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HDAC抑制剂在实验性肝和肾纤维化中的作用。
组蛋白去乙酰化酶(Histone deacetylase, HDAC)抑制剂在癌症实验模型中得到了广泛的研究,它们对去乙酰化的抑制已被证明可以调节细胞的存活、增殖、分化和凋亡。这反过来又导致在临床试验中使用各种HDAC抑制剂。近年来,HDAC抑制剂在其他疾病领域的适用性得到了探索,包括纤维化疾病的治疗。伤口愈合受损涉及由肌成纤维细胞控制的细胞外基质的持续沉积和交联,导致肝脏和肾脏纤维化等疾病;这两种疾病都有大量未满足的医疗需求,对世界各地的卫生预算构成负担。我们根据目前对HDAC抑制剂在实验动物模型和体外纤维化模型中的了解,概述了HDAC抑制剂治疗肝和肾纤维化的潜在用途。
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