M1 macrophage mediated increased reactive oxygen species (ROS) influence wound healing via the MAPK signaling in vitro and in vivo
M1 macrophage mediated increased reactive oxygen species (ROS) influence wound healing via the MAPK signaling in vitro and in vivo
复制标题
DOI：
10.1016/j.taap.2019.01.022
复制
发表时间：
2019-03-01
影响因子：
3.8
通讯作者：
Han, Bang-Min
中科院分区：
文献类型：
--
作者：
Deng, Zheng;Shi, Fei;Han, Bang-Min
前列腺素激光切除术（TmLRP）是治疗良性前列腺增生（BPH）的主要方法，但术后并发症严重影响患者的生活质量。本研究的目的是探讨M1巨噬细胞分泌的活性氧簇（ROS）对前列腺伤口愈合的影响，以及丝裂原活化蛋白激酶信号传导在这一过程中的作用。采用巨噬细胞与前列腺上皮细胞或间质细胞建立体外共培养模型。通过标准分析评估细胞增殖、迁移、凋亡、MAPK通路相关基因表达水平。此外，通过对比格犬进行TmLRP，并用N-乙酰基-L-半胱氨酸（NAC）和/或安慰剂治疗，在比格犬中建立了体内椎间盘切除术模型。在两组中，除了巨噬细胞极化、氧化应激水平和MAPK通路相关蛋白表达之外，还对伤口愈合和再上皮化进行组织病理学分析。与M1样巨噬细胞共培养的前列腺上皮细胞和间质细胞经MAPK激活后，细胞内ROS水平显著升高，影响细胞增殖、迁移和凋亡，延缓伤口愈合过程。通过阻断或清除巨噬细胞分泌的ROS，前列腺细胞的细胞功能和伤口愈合能力得以恢复。在比格犬模型中，增加的ROS水平损害细胞功能，并且适当地去除ROS加速伤口愈合过程。
Thulium laser resection of the prostate (TmLRP), a major treatment for benign prostatic hyperplasia (BPH), has several postoperative complications that affect the patients' quality of life. The aim of this study was to investigate the effect of the M1 macrophage-secreted reactive oxygen species (ROS) on prostatic wound healing, and the role of MAPK signaling in this process. A co-culture model in vitro was established using macrophages and prostate epithelial or stromal cells. Cell proliferation, migration, apoptosis, MAPK pathway-related gene expression levels were evaluated by standard assays. In addition, an in vivo model of prostatectomy was established in beagles by subjecting them to TmLRP, and were either treated with N-acetyl-L-cysteine (NAC) and or placebo. Wound healing and re-epithelialization were analyzed histopathologically in both groups, in addition to macrophage polarization, oxidative stress levels and MAPK pathway-related proteins expressions. Intracellular ROS levels were significantly increased in the prostate epithelial and stromal cells following co-culture with M1-like macrophages and H2O2 exposure via MAPK activation, which affected their proliferation, migration and apoptosis, and delayed the wound healing process. The cellular functions and wound healing capacity of the prostate cells were restored by blocking or clearing the macrophage-secreted ROS. In the beagle model, increased ROS levels impaired cellular functions, and appropriate removing ROS accelerated the wound healing process.