Basement membranes are extracellular matrix sheets separating tissue layers and providing mechanical support, and collagen IV (Col4) is their most abundant structural protein. Although basement membranes are repaired after damage, little is known about repair, including whether and how damage is detected, what cells repair the damage, and how repair is controlled to avoid fibrosis. Using the intestinal basement membrane of adult Drosophila as a model, we show that after basement membrane damage, there is a sharp increase in enteroblasts transiently expressing Col4, termed “matrix mender” cells. Enteroblast-derived Col4 is specifically required for matrix repair. The increase in matrix mender cells requires the mechanosensitive ion channel Piezo, expressed in intestinal stem cells. Matrix menders are induced by the loss of matrix stiffness, as specifically inhibiting Col4 crosslinking is sufficient for Piezo-dependent induction of matrix mender cells. Our data suggest that epithelial stem cells control basement membrane integrity by monitoring stiffness.

中文翻译：

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基体刚度的压电依赖性监测产生修复基底膜的瞬时细胞

基底膜是分离组织层并提供机械支撑的细胞外基质片，胶原蛋白 IV （Col4） 是它们最丰富的结构蛋白。尽管基底膜在损伤后会得到修复，但对修复知之甚少，包括是否以及如何检测损伤、哪些细胞修复损伤以及如何控制修复以避免纤维化。以成年果蝇的肠道基底膜为模型，我们表明在基底膜损伤后，瞬时表达 Col4 的成肠细胞急剧增加，称为“基质修复器”细胞。肠母细胞衍生的 Col4 是基质修复特别需要的。基质修补细胞的增加需要在肠道干细胞中表达的机械敏感离子通道压电。基质修补剂是由基质刚度的丧失诱导的，因为特异性抑制 Col4 交联足以对基质修补剂细胞进行压电依赖性诱导。我们的数据表明，上皮干细胞通过监测刚度来控制基底膜完整性。