Reappearance of an embryonic pattern of fibronectin splicing during wound healing in the adult rat.
Reappearance of an embryonic pattern of fibronectin splicing during wound healing in the adult rat.
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DOI：
10.1083/jcb.109.2.903
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发表时间：
1989-08
期刊：
影响因子：
--
通讯作者：
Hynes RO
中科院分区：
文献类型：
--
作者：
Ffrench-Constant C;Van de Water L;Dvorak HF;Hynes RO
粘附细胞外基质糖蛋白纤连蛋白（FN）被认为在与伤口愈合相关的细胞迁移中发挥重要作用。免疫定位研究表明，伤口愈合过程中含有丰富的 FN；然而，这些研究无法定义 FN 合成的细胞位点，也无法区分由初级基因转录本的选择性剪接产生的不同且可能功能不同的 FN 形式。为了研究伤口愈合过程中 FN 合成和剪接的这些问题，我们使用片段特异性探针对成年大鼠皮肤愈合伤口进行了原位杂交。我们发现受伤后伤口底部的细胞以及伤口侧面下方的肌肉和真皮中 FN 基因的表达水平增加。然而有趣的是，这些区域中 FN mRNA 的剪接模式是不同的。在邻近的真皮和肌肉中，剪接模式与正常成年大鼠皮肤中观察到的剪接模式保持相同，三个剪接片段中的两个（EIIIA 和 EIIIB）被排除在 FN mRNA 之外。相反，这两个片段包含在伤口底部细胞中的 FN mRNA 中。因此，该区域的 mRNA 剪接模式与早期胚胎发生过程中发现的模式相同。伤口愈合过程中 FN 剪接模式类似于胚胎模式的发现表明，在伤口愈合过程中可以使用选择性剪接作为生成 FN 形式的机制，这种形式在功能上可能更适合与组织修复相关的细胞迁移和增殖。
The adhesive extracellular matrix glycoprotein fibronectin (FN) is thought to play an important role in the cell migration associated with wound healing. Immunolocalization studies show abundant FN in healing wounds; however, these studies cannot define the cellular site(s) of FN synthesis, nor do they distinguish the different and potentially functionally distinct forms of FN that can arise from alternative splicing of the primary gene transcript. To examine these questions of FN synthesis and splicing during wound healing, we have performed in situ hybridization with segment-specific probes on healing wounds in adult rat skin. We find that the FN gene is expressed at increased levels after wounding both in the cells at the base of the wound and in subjacent muscle and dermis lateral to the wound. Interestingly, however, the pattern of splicing of FN mRNA was different in these areas. In adjacent dermis and muscle, the splicing pattern remains identical with that seen in normal adult rat skin, with two of the three spliced segments (EIIIA and EIIIB) excluded from FN mRNA. In contrast, these two segments are included in the FN mRNA present in the cells at the base of the wound. As a result, the mRNA in this region is spliced in a pattern identical with that found during early embryogenesis. The finding that the pattern of FN splicing during wound healing resembles an embryonic pattern suggests that alternative splicing may be used during wound healing as a mechanism to generate forms of FN that may be functionally more appropriate for the cell migration and proliferation associated with tissue repair.