PDF(Sci-hub)
Abstract：
Basement membranes are highly specialized extracellular matrices. More than providing scaffolds, basement membranes are recognized as dynamic and versatile structures that modulate cellular responses to regulate tissue development, function, and repair. Increasing evidence suggests that, in addition to providing structural support to adjacent cells, basement membranes serve as reservoirs and modulators of growth factors that direct and fine-tune cellular functions. Since the corneal stroma is avascular and has a relatively low keratocyte density, it\'s likely that the corneal BM is different in composition from the BMs in other tissues. BMs are composed of a diverse assemblage of extracellular molecules, some of which are likely specific to the tissue where they function; but in general they are composed of four primary components-collagens, laminins, heparan sulfate proteoglycans, and nidogens-in addition to other components such as thrombospondin-1, matrilin-2, and matrilin-4 and fibronectin. Severe injuries to the cornea, including infection, surgery, and trauma, may trigger the development of myofibroblasts and fibrosis in the normally transparent connective tissue stroma. Ultrastructural studies have demonstrated that defective epithelial basement membrane (EBM) regeneration after injury to the cornea underlies the development of myofibroblasts from both bone marrow- and keratocyte-derived precursor cells. Defective EBM permits epithelium-derived and tear-derived transforming growth factor beta (TGF-β), platelet-derived growth factor (PDGF), and possibly other modulators, to penetrate the stroma at sustained levels necessary to drive the development and persistence of vimentin + alpha-smooth muscle actin + desmin+ (V + A + D+) mature myofibroblasts. A recent discovery that has contributed to our understanding of haze development is that keratocytes and corneal fibroblasts produce critical EBM components, such as nidogen-1, nidogen-2 and perlecan, that are essential for complete regeneration of a normal EBM once laminin secreted by epithelial cells self-polymerizes into a nascent EBM. Mature myofibroblasts that become established in the anterior stroma are a barrier to keratocyte/corneal fibroblast contributions to the nascent EBM. These myofibroblasts, and the opacity they produce, often persist for months or years after the injury. Transparency is subsequently restored if the EBM is fully regenerated, myofibroblasts are deprived of TGF-β and undergo apoptosis, and keratocytes reoccupy the anterior stroma and reabsorb the disordered extracellular matrix.
摘要：
基底膜是高度特化的细胞外基质。不仅仅是提供脚手架，基底膜被认为是动态和通用的结构，调节细胞反应，调节组织发育，函数,和修复。越来越多的证据表明,除了为相邻的细胞提供结构支持，基底膜是指导和微调细胞功能的生长因子的储库和调节剂。由于角膜基质是无血管的，并且角膜细胞密度相对较低，角膜BM的成分可能与其他组织的BM不同。BMs由不同的细胞外分子组成，其中一些可能特定于它们发挥作用的组织；但一般来说，它们由四种主要成分-胶原蛋白组成，层粘连蛋白,硫酸乙酰肝素蛋白聚糖，和巢蛋白-除了其他成分，如血小板反应蛋白-1，苦参素-2和苦参素-4和纤连蛋白。角膜严重受伤,包括感染,手术,和创伤，可能在正常透明的结缔组织基质中引发肌成纤维细胞和纤维化的发展。超微结构研究表明，角膜损伤后上皮基底膜（EBM）再生缺陷是骨髓和角膜细胞衍生的前体细胞形成肌成纤维细胞的基础。有缺陷的EBM允许上皮衍生和泪液衍生的转化生长因子β（TGF-β），血小板衍生生长因子(PDGF),可能还有其他调制器，以驱动波形蛋白α-平滑肌肌动蛋白desmin（VAD）成熟肌成纤维细胞的发育和持续所需的持续水平穿透基质。最近的一项发现有助于我们对雾霾发展的理解是，角膜细胞和角膜成纤维细胞产生关键的EBM成分，例如nidogen-1，nidogen-2和perlecan，一旦上皮细胞分泌的层粘连蛋白自我聚合成新生的EBM，这对于正常EBM的完全再生至关重要。在前基质中建立的成熟肌成纤维细胞是角膜细胞/角膜成纤维细胞对新生EBM的贡献的屏障。这些肌成纤维细胞，以及它们产生的不透明度，通常在受伤后持续数月或数年。如果完全重新生成EBM，透明度将随后恢复，肌成纤维细胞被剥夺TGF-β并经历凋亡，角膜细胞重新占据前基质并重新吸收无序的细胞外基质。
