Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN 37240-7935, USA.
Center for Matrix Biology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
J Cell Sci. 2019 Apr 8;132(7):jcs226860. doi: 10.1242/jcs.226860.
Basement membranes are an ancient form of animal extracellular matrix. As important structural and functional components of tissues, basement membranes are subject to environmental damage and must be repaired while maintaining functions. Little is known about how basement membranes get repaired. This paucity stems from a lack of suitable models for analyzing such repair. Here, we show that dextran sodium sulfate (DSS) directly damages the gut basement membrane when fed to adult DSS becomes incorporated into the basement membrane, promoting its expansion while decreasing its stiffness, which causes morphological changes to the underlying muscles. Remarkably, two days after withdrawal of DSS, the basement membrane is repaired by all measures of analysis. We used this new damage model to determine that repair requires collagen crosslinking and replacement of damaged components. Genetic and biochemical evidence indicates that crosslinking is required to stabilize the newly incorporated repaired Collagen IV rather than to stabilize the damaged Collagen IV. These results suggest that basement membranes are surprisingly dynamic.
基底膜是一种古老的动物细胞外基质形式。作为组织的重要结构和功能组成部分，基底膜会受到环境损伤，必须在维持功能的同时进行修复。目前人们对基底膜如何修复知之甚少。这种缺乏源自于缺乏合适的模型来分析这种修复。在这里，我们表明，葡聚糖硫酸钠（DSS）在喂食成年动物时会直接损伤肠道基底膜，DSS 会被整合到基底膜中，促进其扩张，同时降低其刚性，从而导致下面肌肉的形态发生变化。值得注意的是，在停止使用 DSS 两天后，基底膜通过所有分析手段都得到了修复。我们使用这种新的损伤模型来确定修复需要胶原交联和受损成分的替换。遗传和生化证据表明，交联是为了稳定新掺入的修复型胶原 IV，而不是稳定受损的胶原 IV。这些结果表明，基底膜具有惊人的动态性。
