Origin and function of myofibroblasts in kidney fibrosis.
Origin and function of myofibroblasts in kidney fibrosis.
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肌成纤维细胞与器官纤维化有关，但其确切来源和功能作用仍不清楚。我们采用多只基因工程小鼠来追踪、绘制命运图和消融细胞，以确定肾纤维化中肌成纤维细胞的来源和功能。这种全面的分析确定了肌成纤维细胞的总池是分开的，其中50%通过增殖来自局部驻留的成纤维细胞。非增殖性肌成纤维细胞通过骨髓分化（35%）、内皮向间充质转化（EndMT）程序（10%）和上皮向间充质转化（EMT）程序（5%）获得。αSMA+细胞中Tgfbr 2的特异性缺失揭示了该途径在通过分化募集肌成纤维细胞中的重要性。使用遗传小鼠模型和命运映射策略，我们确定血管周细胞可能不会导致肌成纤维细胞或纤维化的出现。这项研究表明，需要靶向不同的途径，以显着抑制肾纤维化中肌成纤维细胞的复合积累。
Myofibroblasts are associated with organ fibrosis but their precise origin and functional role remain unknown. We employed multiple genetically engineered mice to track, fate-map and ablate cells to determine the source and function of myofibroblasts in kidney fibrosis. Such comprehensive analysis identified that the total pool of myofibroblasts is split, with 50% arising from local resident fibroblasts via proliferation. The non-proliferating myofibroblasts derive via differentiation from bone marrow (35%), endothelial to mesenchymal transition (EndMT) program (10%) and epithelial to mesenchymal transition (EMT) program (5%). Specific deletion of Tgfbr2 in αSMA+ cells revealed the importance of this pathway in recruitment of myofibroblasts via differentiation. Using genetic mouse models and fate-mapping strategy we determined that vascular pericytes likely do not contribute to the emergence of myofibroblasts or fibrosis. This study suggests that targeting diverse pathways is required to significantly inhibit composite accumulation of myofibroblasts in kidney fibrosis.
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影响因子：
1.5
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Chytil, A;Magnuson, MA;Moses, HL
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