Evidence that fibroblasts derive from epithelium during tissue fibrosis.
Evidence that fibroblasts derive from epithelium during tissue fibrosis.
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DOI：
10.1172/jci15518
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发表时间：
2002-08
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影响因子：
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通讯作者：
M. Iwano;David Plieth;T. Danoff;Chengsen Xue;H. Okada;E. Neilson
中科院分区：
文献类型：
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作者：
M. Iwano;David Plieth;T. Danoff;Chengsen Xue;H. Okada;E. Neilson
间质成纤维细胞是肾、肺和肝中器官纤维化的主要效应细胞。虽然有些人认为成人组织中的成纤维细胞只不过是胚胎发育中存活的原始间充质细胞，但它们与间充质细胞的不同之处在于成纤维细胞特异性蛋白-1（FSP 1）的独特表达。这种差异引起了关于其起源的问题。使用骨髓嵌合体和转基因报告小鼠，我们在这里表明，间质肾成纤维细胞来自两个来源。少量FSP 1（+）、CD 34（-）成纤维细胞从骨髓迁移至正常间质间隙。然而，更令人惊讶的是，FSP 1（+）成纤维细胞也在肾纤维化过程中通过局部上皮-间充质转化（EMT）大量出现。两种成纤维细胞群体均表达I型胶原蛋白，并在组织纤维化期间通过细胞分裂而扩增。我们的研究结果表明，大量的器官成纤维细胞出现通过一种新的逆转上皮细胞的命运的方向。作为一般机制，这种命运的变化突出了病理条件下成体组织中分化细胞的潜在可塑性。
Interstitial fibroblasts are principal effector cells of organ fibrosis in kidneys, lungs, and liver. While some view fibroblasts in adult tissues as nothing more than primitive mesenchymal cells surviving embryologic development, they differ from mesenchymal cells in their unique expression of fibroblast-specific protein-1 (FSP1). This difference raises questions about their origin. Using bone marrow chimeras and transgenic reporter mice, we show here that interstitial kidney fibroblasts derive from two sources. A small number of FSP1(+), CD34(-) fibroblasts migrate to normal interstitial spaces from bone marrow. More surprisingly, however, FSP1(+) fibroblasts also arise in large numbers by local epithelial-mesenchymal transition (EMT) during renal fibrogenesis. Both populations of fibroblasts express collagen type I and expand by cell division during tissue fibrosis. Our findings suggest that a substantial number of organ fibroblasts appear through a novel reversal in the direction of epithelial cell fate. As a general mechanism, this change in fate highlights the potential plasticity of differentiated cells in adult tissues under pathologic conditions.