The Function of SPARC as a Mediator of Fibrosis.

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.

纤维化是许多不同疾病的常见终点，例如高血压、糖尿病、肝硬化以及那些与慢性炎症相关的疾病。纤维化的特征是细胞外基质过度沉积，干扰正常组织结构和功能。众多研究报道在纤维化组织中富含半胱氨酸的酸性分泌蛋白（SPARC）表达增加。SPARC是一种由几种不同细胞类型分泌到细胞外基质中的43 kDa胶原蛋白结合蛋白，已在体外显示出抗增殖和抗黏附作用。SPARC是一种基质细胞蛋白，这意味着它被分泌到细胞外空间但不具有结构功能。相反，SPARC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以及人类纤维化组织中，据报道在许多组织包括心脏、肺、肾、肝、真皮、肠道和眼睛中SPARC表达升高。在这篇综述中，我们将总结当前研究，这些研究检测了SPARC在各种纤维化动物模型以及人类组织中的表达和功能重要性。尽管SPARC在纤维化中的细胞机制仍有待完全阐明，但这里总结的研究为进一步探索SPARC作为减少纤维化的潜在靶点的功效提供了动力。