巨噬细胞 Wnt7b 对于肾脏修复和再生至关重要。
Macrophage Wnt7b is critical for kidney repair and regeneration.
机构信息
Laboratory of Inflammation Research, Renal Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
出版信息
Proc Natl Acad Sci U S A. 2010 Mar 2;107(9):4194-9. doi: 10.1073/pnas.0912228107. Epub 2010 Feb 16.
Abstract
Macrophages are required for tissue homeostasis through their role in regulation of the immune response and the resolution of injury. Here we show, using the kidney as a model, that the Wnt pathway ligand Wnt7b is produced by macrophages to stimulate repair and regeneration. When macrophages are inducibly ablated from the injured kidney, the canonical Wnt pathway response in kidney epithelial cells is reduced. Furthermore, when Wnt7b is somatically deleted in macrophages, repair of injury is greatly diminished. Finally, injection of the Wnt pathway regulator Dkk2 enhances the repair process and suggests a therapeutic option. Because Wnt7b is known to stimulate epithelial responses during kidney development, these findings suggest that macrophages are able to rapidly invade an injured tissue and reestablish a developmental program that is beneficial for repair and regeneration.
摘要
巨噬细胞通过调节免疫反应和损伤修复来维持组织内稳态。在这里，我们以肾脏为模型，发现 Wnt 通路配体 Wnt7b 由巨噬细胞产生，以刺激修复和再生。当诱导性地从受损肾脏中清除巨噬细胞时，肾脏上皮细胞中的经典 Wnt 通路反应会减少。此外，当巨噬细胞中的 Wnt7b 被体细胞删除时，损伤的修复大大减少。最后，注射 Wnt 通路调节剂 Dkk2 可增强修复过程，并提供一种治疗选择。由于已知 Wnt7b 在肾脏发育过程中刺激上皮反应，这些发现表明巨噬细胞能够迅速浸润受损组织，并重新建立有利于修复和再生的发育程序。
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