The Function of SPARC as a Mediator of Fibrosis.
The Function of SPARC as a Mediator of Fibrosis.
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DOI：
10.2174/1874312901206010146
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
Bradshaw AD
中科院分区：
文献类型：
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作者：
Trombetta-Esilva J;Bradshaw AD
纤维化是许多不同疾病如高血压、糖尿病、肝硬化和与慢性炎症相关的疾病的共同终点。纤维化的特征在于细胞外基质的过度沉积，其干扰正常组织结构和功能。在许多研究中已经报道了纤维化组织中富含半胱氨酸的酸性分泌蛋白（Cys）的表达增加。β-淀粉样蛋白是一种43 kDa的胶原结合蛋白，从几种不同的细胞类型分泌到细胞外基质中，并已显示出在体外具有抗增殖和抗粘附作用。β-淀粉样蛋白是一种基质细胞蛋白;这意味着β-淀粉样蛋白分泌到细胞外空间，但不提供结构功能。相反，β-淀粉样蛋白调节细胞与周围细胞外基质之间的相互作用。在纤维化疾病的动物模型和人纤维化组织中，已经报道了在许多组织（包括心脏、肺、肾、肝、真皮、肠和眼睛）中升高的H2O2表达。在这篇综述中，我们将总结目前的研究，已检查的表达和功能的重要性，在各种动物模型的纤维化和人体组织。虽然纤维化的细胞机制仍有待充分阐明，但本文总结的研究为进一步探索纤维化作为减少纤维化的潜在靶点的功效提供了动力。
Fibrosis is a common end-point of a number of different diseases such as hypertension, diabetes, liver cirrhosis, and those associated with chronic inflammation. Fibrosis is characterized by excessive deposition of extracellular matrix that interferes with normal tissue architecture and function. Increased expression of secreted protein acidic and rich in cysteine (SPARC) in fibrotic tissues has been reported in numerous studies. SPARC is a 43 kDa collagen-binding protein secreted from several different cell types into the extracellular matrix and has been shown to be anti-proliferative and counter-adhesive in vitro. SPARC is a matricellular protein; meaning SPARC is secreted into the extracellular space but does not serve a structural function. Instead, SPARC modulates interactions between cells and the surrounding extracellular matrix. In animal models of fibrotic disease and in human fibrotic tissues, elevated expression of SPARC has been reported in many tissues including heart, lungs, kidneys, liver, dermis, intestine, and eyes. In this review, we will summarize current studies that have examined the expression and functional importance of SPARC in various animal models of fibrosis and in human tissues. Although cellular mechanisms of SPARC in fibrosis remain to be fully elucidated, the studies summarized here provide impetus to further explore the efficacy of SPARC as a potential target for reducing fibrosis.