- Macrophages induce AKT/β-catenin-dependent Lgr5
Macrophages induce AKT/β-catenin-dependent Lgr5
Nature communications (2017-03-28)
Xusheng Wang, Haiyan Chen, Ruiyun Tian, Yiling Zhang, Marina S Drutskaya, Chengmei Wang, Jianfeng Ge, Zhimeng Fan, Deqiang Kong, Xiaoxiao Wang, Ting Cai, Ying Zhou, Jingwen Wang, Jinmei Wang, Shan Wang, Zhihai Qin, Huanhuan Jia, Yue Wu, Jia Liu, Sergei A Nedospasov, Edward E Tredget, Mei Lin, Jianjun Liu, Yuyang Jiang, Yaojiong Wu
PMID28345588
ABSTRACT
Skin stem cells can regenerate epidermal appendages; however, hair follicles (HF) lost as a result of injury are barely regenerated. Here we show that macrophages in wounds activate HF stem cells, leading to telogen-anagen transition (TAT) around the wound and de novo HF regeneration, mostly through TNF signalling. Both TNF knockout and overexpression attenuate HF neogenesis in wounds, suggesting dose-dependent induction of HF neogenesis by TNF, which is consistent with TNF-induced AKT signalling in epidermal stem cells in vitro. TNF-induced β-catenin accumulation is dependent on AKT but not Wnt signalling. Inhibition of PI3K/AKT blocks depilation-induced HF TAT. Notably, Pten loss in Lgr5