Chakravarti Shukti, Enzo Elena, Rocha Monteiro de Barros Maithê, Maffezzoni Maria Benedetta Rizzarda, Pellegrini Graziella
Department of Ophthalmology and Department of Pathology, Grossman School of Medicine, New York University, New York, NY, USA; email:
Center for Regenerative Medicine "Stefano Ferrari," University of Modena and Reggio Emilia, Modena, Italy; email:
Annu Rev Genomics Hum Genet. 2022 Aug 31;23:193-222. doi: 10.1146/annurev-genom-083117-021702. Epub 2022 May 10.
Metazoans have evolved to produce various types of extracellular matrix (ECM) that provide structural support, cell adhesion, cell-cell communication, and regulated exposure to external cues. Epithelial cells produce and adhere to a specialized sheet-like ECM, the basement membrane, that is critical for cellular homeostasis and tissue integrity. Mesenchymal cells, such as chondrocytes in cartilaginous tissues and keratocytes in the corneal stroma, produce a pericellular matrix that presents optimal levels of growth factors, cytokines, chemokines, and nutrients to the cell and regulates mechanosensory signals through specific cytoskeletal and cell surface receptor interactions. Here, we discuss laminins, collagen types IV and VII, and perlecan, which are major components of these two types of ECM. We examinegenetic defects in these components that cause basement membrane pathologies such as epidermolysis bullosa, Alport syndrome, rare pericellular matrix-related chondrodysplasias, and corneal keratoconus and discuss recent advances in cell and gene therapies being developed for some of these disorders.
后生动物已经进化出产生各种类型的细胞外基质（ECM），这些细胞外基质提供结构支持、细胞粘附、细胞间通讯以及对外部信号的调节性暴露。上皮细胞产生并附着于一种特殊的片状细胞外基质，即基底膜，它对细胞内稳态和组织完整性至关重要。间充质细胞，如软骨组织中的软骨细胞和角膜基质中的角膜细胞，产生一种细胞周围基质，该基质为细胞提供最佳水平的生长因子、细胞因子、趋化因子和营养物质，并通过特定的细胞骨架和细胞表面受体相互作用调节机械感觉信号。在这里，我们讨论层粘连蛋白、IV型和VII型胶原蛋白以及基底膜聚糖，它们是这两种类型细胞外基质的主要成分。我们研究了这些成分中的基因缺陷，这些缺陷会导致基底膜病变，如大疱性表皮松解症、阿尔波特综合征、罕见的与细胞周围基质相关的软骨发育不全以及圆锥角膜，并讨论了针对其中一些疾病正在开发的细胞和基因疗法的最新进展。
