Fibrocytes can be reprogrammed to promote tissue remodeling capacity of dermal fibroblasts
Fibrocytes can be reprogrammed to promote tissue remodeling capacity of dermal fibroblasts
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DOI：
10.1007/s11010-010-0524-4
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发表时间：
2010-11-01
影响因子：
4.3
通讯作者：
Ghahary, Aziz
中科院分区：
文献类型：
--
作者：
Medina, Abelardo;Ghahary, Aziz
成纤维细胞在参与组织纤维化和重塑的伤口愈合过程中发挥着关键作用。然而，目前尚不清楚哪些因素激活成纤维细胞反应的多样性以及这一决策过程是如何进行的。先前的报告表明，伤口环境会刺激循环前体细胞转化为纤维细胞。这些促纤维化细胞促进常驻成纤维细胞产生胶原蛋白。相反，尚未鉴定出具有可与纤维细胞竞争的抗纤维形成特征的招募细胞。该报告描述了通过改变培养条件诱导的纤维细胞的新型转分化过程。重新编程的纤维细胞显着增加了真皮成纤维细胞的细胞增殖和 MMP-1 表达。 MMP-1 上调与细胞转化后的纤维细胞数量直接相关。体外和体内结果证实，TGF-β剥夺在这种新型纤维细胞分化途径中发挥着重要作用。我们的研究结果表明，改变纤维细胞的承诺，可以成倍地刺激真皮成纤维细胞的组织重塑能力。这些结果将开辟新的研究方法，以了解细胞转分化和局部环境不仅在皮肤伤口愈合过程中的作用，而且在其他几种纤维细胞相关疾病如肺纤维化、哮喘、肝硬化、慢性胰腺炎和动脉粥样硬化中的作用。
Fibroblasts play a pivotal role in wound healing process participating in both tissue fibrosis and remodeling. However, it remains unclear which factors activate such diversity of fibroblast responses and how this decision-making process is made. Previous reports have demonstrated that wound milieu stimulates the transformation of circulating precursor cells into fibrocytes. These pro-fibrogenic cells promote the collagen production by resident fibroblasts. Conversely, recruited cells with anti-fibrogenic profile that can compete with fibrocytes have not been identified. This report describes a novel transdifferentiation process of fibrocytes induced by changing culture conditions. The reprogrammed fibrocytes markedly increased cell proliferation and MMP-1 expression in dermal fibroblasts. The MMP-1 up-regulation was directly related to the number of fibrocytes that followed this cell transformation. In vitro and in vivo results have confirmed that TGF-beta deprivation plays an important role in this novel fibrocyte differentiation pathway. Our findings demonstrate that, changing the fibrocyte commitment, it is possible to exponentially stimulate the tissue remodeling capacity of dermal fibroblasts. These results will open new research approaches to understand the role of cell transdifferentiation and local environment not only in the wound healing process of skin, but also in several other fibrocyte-associated diseases such as lung fibrosis, asthma, liver cirrhosis, chronic pancreatitis, and atherosclerosis.