期刊
TOHOKU JOURNAL OF EXPERIMENTAL MEDICINE
卷 236, 期 3, 页码 209-217出版社
TOHOKU UNIV MEDICAL PRESS
DOI: 10.1620/tjem.236.209
关键词
lung fibroblasts; radiation-induced lung injury; transwell co-culture; umbilical cord mesenchymal stem cells; Wnt/beta-catenin signaling
Radiation-induced lung injury (RILI) limits the benefits of radiotherapy in patients with lung cancer. Radiation-induced differentiation of lung fibroblasts to myofibroblasts plays a key role in RILI. Recent studies have shown that mesenchymal stem cells (MSCs) can protect against lung fibrosis and that Wnt/beta-catenin signaling is involved in fibrotic processes. In the present study, we explored the therapeutic potential of human umbilical cord MSCs (HUMSCs) for preventing radiation-induced differentiation of human lung fibroblasts (HLFs) to myofibroblasts. There are two advantages in the use of HUMSCs; namely, they are easily obtained and have low immunogenicity. Irradiated HLFs were co-cultured with HUMSCs. Expression of alpha-smooth muscle actin (alpha-SMA), a myofibroblast marker, was measured by Western blot analysis and immunohistochemistry. Irradiation (X-rays, 5 Gy) induced the differentiation of HLFs into myofibroblasts, which was inhibited by co-culture with HUMSCs. Irradiation also caused activation of the canonical Wnt/beta-catenin signaling in HLFs, as judged by increased phosphorylation of glycogen synthase kinase 3 beta, nuclear accumulation of beta-catenin, and elevated levels of Wnt-inducible signaling protein-1 (WISP-1) in the conditioned medium. However, co-culture with HUMSCs attenuated the radiation-induced activation of the Wnt/beta-catenin signaling. We also measured the expression of FRAT1 that can enhance the Wnt/beta-catenin signaling by stabilizing beta-catenin. Co-culture with HUMSCs decreased FRAT1 protein levels in irradiated nHLFs. Thus, co-culture with HUMSCs attenuated the radiation-induced activation of Wnt/beta-catenin signaling in HLFs, thereby inhibiting myofibroblastic differentiation of HLFs. Wnt/beta-catenin signaling is a potential therapeutic target for limiting RILI in patients receiving radiotherapy for lung cancer.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据