Fibrocytes are not an essential source of type I collagen during lung fibrosis.
Fibrocytes are not an essential source of type I collagen during lung fibrosis.
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DOI：
10.4049/jimmunol.1400753
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发表时间：
2014-11-15
期刊：
影响因子：
--
通讯作者：
Kim KK
中科院分区：
文献类型：
--
作者：
Kleaveland KR;Velikoff M;Yang J;Agarwal M;Rippe RA;Moore BB;Kim KK
进行性纤维化涉及活化的胶原生成间充质细胞的堆积。纤维细胞是一种具有间充质特征的造血细胞，在纤维化过程中具有独特的关键功能。纤维细胞被认为是纤维化过程中I型胶原沉积的重要直接贡献者，这主要是基于命运图研究。为了确定造血细胞来源的I型胶原在纤维化形成中的功能贡献，我们利用双转基因系统在广泛的造血细胞群体中特异性地删除了I型胶原基因。这些小鼠表现出强烈的纤维化反应，类似于用博莱霉素损伤的仔鼠基因型对照小鼠，这表明纤维细胞不是I型胶原的必要来源。利用胶原促进剂GFP小鼠，我们发现纤维细胞表达I型胶原。然而，确认I型胶原基因缺失的纤维细胞很容易检测到细胞内的I型胶原，这表明从邻近细胞摄取的胶原是纤维细胞胶原的主要来源。总而言之，这些结果澄清了几个关于纤维细胞对胶原沉积的直接贡献的似乎相互矛盾的报道。
Progressive fibrosis involves accumulation of activated collagen producing mesenchymal cells. Fibrocytes are hematopoietic-derived cells with mesenchymal features that potentially have a unique and critical function during fibrosis. Fibrocytes have been proposed as an important direct contributor of type I collagen deposition during fibrosis based largely on fate-mapping studies. To determine the functional contribution of hematopoietic cell-derived type I collagen to fibrogenesis we utilize a double transgenic system to specifically delete the type I collagen gene across a broad population of hematopoietic cells. These mice develop a robust fibrotic response similar to littermate genotype control mice injured with bleomycin indicating that fibrocytes are not a necessary source of type I collagen. Using collagen-promoter GFP mice we find that fibrocytes express type I collagen. However, fibrocytes with confirmed deletion of the type I collagen gene have readily detectable intracellular type I collagen indicating that uptake of collagen from neighboring cells account for much of the fibrocyte collagen. Collectively these results clarify several seemingly conflicting reports regarding the direct contribution of fibrocytes to collagen deposition.
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DOI：
10.1073/pnas.94.12.6307
发表时间：
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