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/jci200215518
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发表时间：
2002-08-01
影响因子：
15.9
通讯作者：
Neilson, EG
中科院分区：
文献类型：
--
作者：
Iwano, M;Plieth, D;Neilson, EG
间质成纤维细胞是肾脏、肺和肝脏器官纤维化的主要效应细胞。虽然有些人认为成体组织中的成纤维细胞只不过是胚胎发育中幸存下来的原始间充质细胞，但它们与间充质细胞的不同之处在于其独特的成纤维细胞特异性蛋白 1 (FSP1) 表达。这种差异引发了对其起源的疑问。使用骨髓嵌合体和转基因报告小鼠，我们在此表明间质肾成纤维细胞有两个来源。少量FSP1(+)、CD34(-)成纤维细胞从骨髓迁移至正常间隙。然而，更令人惊讶的是，FSP1(+)成纤维细胞在肾纤维化过程中也通过局部上皮间质转化(EMT)大量产生。两种成纤维细胞群都表达 I 型胶原蛋白，并在组织纤维化过程中通过细胞分裂而扩展。我们的研究结果表明，大量的器官成纤维细胞是通过上皮细胞命运方向的新逆转而出现的。作为一种一般机制，这种命运的变化凸显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.