A scar-like lesion is apparent in basement membrane after wound repair in vivo.

A scar-like lesion is apparent in basement membrane after wound repair in vivo.
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DOI:
10.1016/j.matbio.2018.07.004
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发表时间:
2018-12
期刊:
Matrix biology : journal of the International Society for Matrix Biology
影响因子:
--
通讯作者:
Page-McCaw A
Page-McCaw A
中科院分区:
其他
文献类型:
--
作者:
Ramos-Lewis W;LaFever KS;Page-McCaw A

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基底膜是动物体内高度保守的片状细胞外基质,位于简单和复杂上皮细胞之下,并包裹肌肉和神经等组织。就像它们所支持的组织一样,基底膜也会因环境的损害而受损。虽然很明显,基底膜在损伤后会修复,但实际上对这一过程一无所知。例如,修复的基底膜与未受损的基底膜相比如何,基底膜成分是否是上皮伤口闭合所必需的,或者修复基底膜是否遵循类似于胚胎基底膜组装的层次结构。在这份报告中,我们解决这些问题,果蝇幼虫表皮的基底膜作为一个模型系统。通过分析四种主要的基底膜蛋白--层粘连蛋白、IV型胶原、串珠素和巢蛋白--我们发现,尽管基底膜在体内机械损伤后一天内修复,但所有四种蛋白组分的增厚和紊乱的基质瘢痕都是明显的。修复受损基底膜的新基质蛋白是由远处的脂肪和肌肉组织提供的,而不是由局部上皮提供的,这些组织为未受伤的基底膜的生长提供基质蛋白。为了确定修复的层次,我们测试了每个基底膜蛋白对其他蛋白的依赖性,以在损伤后并入。为了在损伤后适当地掺入,巢蛋白需要层粘连蛋白,并且串珠素需要IV型胶原蛋白,但令人惊讶的是IV型胶原蛋白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。
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 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 for de novo assembly.
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