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首页> 外文期刊>Cell Reports >Article Tissue-Resident PDGFRαsup+/sup Progenitor Cells Contribute to Fibrosis versus Healing in a Context- and Spatiotemporally Dependent Manner
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Article Tissue-Resident PDGFRαsup+/sup Progenitor Cells Contribute to Fibrosis versus Healing in a Context- and Spatiotemporally Dependent Manner

机译：文章组织驻留PDGFRα + 祖细胞在语境和时空依赖的方式中有助于纤维化与愈合

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摘要

PDGFRαsup+/sup mesenchymal progenitor cells are associated with pathological fibro-adipogenic processes. Conversely, a beneficial role for these cells during homeostasis or in response to revascularization and regeneration stimuli is suggested, but remains to be defined. We studied the molecular profile and function of PDGFRαsup+/sup cells in order to understand the mechanisms underlying their role in fibrosis versus regeneration. We show that PDGFRαsup+/sup cells are essential for tissue revascularization and restructuring through injury-stimulated remodeling of stromal and vascular components, context-dependent clonal expansion, and ultimate removal of pro-fibrotic PDGFRαsup+/sup-derived cells. Tissue ischemia modulates the PDGFRαsup+/sup phenotype toward cells capable of remodeling the extracellular matrix and inducing cell-cell and cell-matrix adhesion, likely favoring tissue repair. Conversely, pathological healing occurs if PDGFRαsup+/sup-derived cells persist as terminally differentiated mesenchymal cells. These studies support a context-dependent “yin-yang” biology of tissue-resident mesenchymal progenitor cells, which possess an innate ability to limit injury expansion while also promoting fibrosis in an unfavorable environment.
机译：PDGFRα + 间充质祖细胞与病理纤维脂肪生成过程有关。相反，提出了在稳态期间或应对血运重建和再生刺激期间这些细胞的有益作用，但仍有待定义。我们研究了PDGFRα + 细胞的分子曲线和功能，以了解其在纤维化中作用的机制与再生的作用。我们表明PDGFRα + 细胞对于组织血运重建和通过损伤刺激的基质和血管成分的重组，背景依赖性克隆膨胀和最终去除促纤维化PDGFRα + / sup>长达细胞。组织缺血调节PDGFRα + 表型朝向能够改造细胞外基质的细胞并诱导细胞 - 细胞和细胞基质粘附，可能是有利于组织修复。相反，如果PDGFRα + 的细胞持续作为末端分化的间充质细胞，则发生病理愈合。这些研究支持组织常规间充质祖细胞的上下文依赖性的“阴阳”生物学，其具有限制损伤突变的先天能力，同时促进不利环境中的纤维化。

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