PDF(Pubmed)
Abstract：
Every organ develops fibrosis that compromises functions in response to infections, injuries, or diseases. The cornea is a relatively simple, avascular organ that offers an exceptional model to better understand the pathophysiology of the fibrosis response. Injury and defective regeneration of the epithelial basement membrane (EBM) or the endothelial Descemet\'s basement membrane (DBM) triggers the development of myofibroblasts from resident corneal fibroblasts and bone marrow-derived blood borne fibrocytes due to the increased entry of TGF beta-1/-2 into the stroma from the epithelium and tears or residual corneal endothelium and aqueous humor. The myofibroblasts, and disordered extracellular matrix these cells produce, persist until the source of injury is removed, the EBM and/or DBM are regenerated, or replaced surgically, resulting in decreased stromal TGF beta requisite for myofibroblast survival. A similar BM injury-related pathophysiology can underly the development of fibrosis in other organs such as skin and lung. The normal liver does not contain traditional BMs but develops sinusoidal endothelial BMs in many fibrotic diseases and models. However, normal hepatic stellate cells produce collagen type IV and perlecan that can modulate TGF beta localization and cognate receptor binding in the space of Dissé. BM-related fibrosis is deserving of more investigation in all organs.
摘要：
每个器官都会发生纤维化，从而损害对感染的反应功能，受伤,或疾病。角膜是一个相对简单的，无血管器官，提供了一个特殊的模型，以更好地了解纤维化反应的病理生理学。上皮基底膜（EBM）或内皮基底膜（DBM）的损伤和再生缺陷会触发肌成纤维细胞从常驻角膜成纤维细胞和骨髓来源的血源性纤维细胞发育，这是由于TGFβ-1/-2从上皮和泪液或残余角膜内皮和房水进入基质的增加。肌成纤维细胞，这些细胞产生的无序的细胞外基质，坚持直到损伤源被移除，再生EBM和/或DBM，或者手术更换，导致肌成纤维细胞存活所需的基质TGFβ降低。类似的BM损伤相关病理生理学可以在其他器官如皮肤和肺中形成纤维化。正常肝脏不包含传统的BMs，但在许多纤维化疾病和模型中会产生窦状内皮BMs。然而,正常的肝星状细胞产生IV型胶原和Perlecan，它们可以调节TGFβ的定位和在Dissé空间中的同源受体结合。BM相关的纤维化值得在所有器官中进行更多的研究。
