文章基本信息

标题：Principles of Cell Circuits for Tissue Repair and Fibrosis
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作者：Miri Adler ; Avi Mayo ; Xu Zhou 等
期刊名称：iScience
印刷版ISSN：2589-0042
出版年度：2020
卷号：23
期号：2
页码：1-25
DOI：10.1016/j.isci.2020.100841
语种：English
出版社：Elsevier
摘要：SummaryTissue repair is a protective response after injury, but repetitive or prolonged injury can lead to fibrosis, a pathological state of excessive scarring. To pinpoint the dynamic mechanisms underlying fibrosis, it is important to understand the principles of the cell circuits that carry out tissue repair. In this study, we establish a cell-circuit framework for the myofibroblast-macrophage circuit in wound healing, including the accumulation of scar-forming extracellular matrix. We find that fibrosis results from multistability between three outcomes, which we term “hot fibrosis” characterized by many macrophages, “cold fibrosis” lacking macrophages, and normal wound healing. This framework clarifies several unexplained phenomena including the paradoxical effect of macrophage depletion, the limited time-window in which removing inflammation leads to healing, and why scar maturation takes months. We define key parameters that control the transition from healing to fibrosis, which may serve as potential targets for therapeutic reduction of fibrosis.Graphical AbstractDisplay OmittedHighlights•A myofibroblast-macrophage circuit for tissue repair shows three physiological states•States correspond to healing, cold fibrosis (lacking macrophages), and hot fibrosis•The circuit explains how a transient/persistent insult leads to healing/fibrosis•The PDGF autocrine loop is a potential target for abrogating fibrosisIn Silico Biology; Systems Biology; Tissue Engineering