Department of Cell and Developmental Biology, Program in Developmental Biology, Center for Matrix Biology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
Department of Cell and Developmental Biology, Program in Developmental Biology, Center for Matrix Biology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
Matrix Biol. 2018 Dec;74:101-120. doi: 10.1016/j.matbio.2018.07.004. Epub 2018 Jul 5.
Basement membrane is a highly conserved sheet-like extracellular matrix in animals, underlying simple and complex epithelia, and wrapping around tissues like muscles and nerves. Like the tissues they support, basement membranes become damaged by environmental insults. Although it is clear that basement membranes are repaired after damage, virtually nothing is known about this process. For example, it is not known how repaired basement membranes compare to undamaged ones, whether basement membrane components are necessary for epithelial wound closure, or whether there is a hierarchy of assembly that repairing basement membranes follow, similar to the hierarchy of assembly of embryonic basement membranes. In this report, we address these questions using the basement membrane of the Drosophila larval epidermis as a model system. By analyzing the four main basement membrane proteins - laminin, collagen IV, perlecan, and nidogen - we find that although basement membranes are repaired within a day after mechanical damage in vivo, thickened and disorganized matrix scars are evident with all four protein components. The new matrix proteins that repair damaged basement membranes are provided by distant adipose and muscle tissues rather than by the local epithelium, the same distant tissues that provide matrix proteins for growth of unwounded epithelial basement membranes. To identify a hierarchy of repair, we tested the dependency of each of the basement membrane proteins on the others for incorporation after damage. For proper incorporation after damage, nidogen requires laminin, and perlecan requires collagen IV, but surprisingly collagen IV does not to depend on laminin. Thus, the rules of basement membrane repair are subtly different than those of de novo assembly.
基底膜是动物中高度保守的片状细胞外基质，位于简单和复杂上皮组织的下方，并围绕肌肉和神经等组织包裹。基底膜与它们所支持的组织一样，会受到环境损伤的破坏。尽管基底膜在受损后会被修复，但实际上人们对这个过程知之甚少。例如，人们不知道修复后的基底膜与未受损的基底膜相比如何，基底膜的组成成分是否对上皮细胞伤口的闭合是必需的，或者是否存在一个类似于胚胎基底膜组装的层次结构，修复基底膜遵循这个层次结构。在本报告中，我们使用果蝇幼虫表皮的基底膜作为模型系统来解决这些问题。通过分析四种主要的基底膜蛋白 - 层粘连蛋白、胶原 IV、perlecan 和巢蛋白 - 我们发现，尽管在体内机械损伤后，基底膜在一天内得到修复，但所有四种蛋白成分都存在明显的增厚和紊乱的基质疤痕。修复受损基底膜的新基质蛋白是由远处的脂肪组织和肌肉组织提供的，而不是由局部上皮组织提供的，这些远处的组织与为未受伤的上皮基底膜生长提供基质蛋白的组织相同。为了确定修复的层次结构，我们测试了每种基底膜蛋白在损伤后对其他蛋白的依赖性。为了正确地在损伤后被整合，巢蛋白需要层粘连蛋白，perlecan 需要胶原 IV，但令人惊讶的是，胶原 IV 并不依赖于层粘连蛋白。因此，基底膜修复的规则与从头组装的规则略有不同。
