Division of Nephrology, Institute of Stem Cell and Regenerative Medicine, Center for Lung Biology, Kidney Research Institute, University of Washington, Seattle, Washington 98109, USA.
Curr Opin Nephrol Hypertens. 2013 Jul;22(4):471-80. doi: 10.1097/MNH.0b013e328362485e.
Pericytes and perivascular fibroblasts have emerged as poorly appreciated yet extensive populations of mesenchymal cells in the kidney that play important roles in homeostasis and responses to injury. This review will update readers on the evolving understanding of the biology of these cells.
Fate mapping has identified pericytes and perivascular fibroblasts as the major source of pathological fibrillar matrix-forming cells in interstitial kidney disease. In other organs similar cells have been described and independent fate mapping indicates that pericytes or perivascular cells are myofibroblast progenitors in multiple organs. Over the last year, new insights into the function of pericytes in kidney homeostasis has been uncovered and new molecular pathways that regulate detachment and their transdifferentiation into pathological myofibroblasts, including Wingless/Int, ephrin, transforming growth factor β, platelet derived growth factor, and Hedgehog signaling pathways, have been reported. In addition provocative studies indicate that microRNAs, which regulate posttranscriptional gene expression, may also play important roles in their transdifferentiation.
Pericytes and perivascular fibroblasts are the major source of pathological collagen fiber-forming cells in interstitial kidney diseases. New avenues of research into their activation and differentiation has identified new drug candidates for the treatment of interstitial kidney disease.
周细胞和血管周围成纤维细胞作为肾脏中未被充分认识但广泛存在的间充质细胞群体,在维持内环境稳定和对损伤的反应中发挥着重要作用。这篇综述将为读者更新对这些细胞生物学的不断发展的认识。
通过对命运图谱的研究,发现周细胞和血管周围成纤维细胞是间质肾脏疾病中病理性纤维状基质形成细胞的主要来源。在其他器官中也有类似的细胞被描述,独立的命运图谱表明,周细胞或血管周围细胞是多个器官中肌成纤维细胞的前体细胞。在过去的一年中,人们对周细胞在肾脏稳态中的功能有了新的认识,并发现了新的分子途径来调节其分离及其向病理性肌成纤维细胞的转分化,包括 Wnt/β-catenin、表皮生长因子、转化生长因子-β、血小板衍生生长因子和 Hedgehog 信号通路。此外,一些有启发性的研究表明,微小 RNA(miRNA)可能在其转分化中也发挥着重要作用,miRNA 通过调节转录后基因表达而起作用。
周细胞和血管周围成纤维细胞是间质肾脏疾病中病理性胶原纤维形成细胞的主要来源。对其激活和分化的新研究途径为治疗间质肾脏疾病提供了新的药物靶点。