2. Academic Validation
  3. 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

  • Toxicol Appl Pharmacol. 2019 Mar 1;366:83-95. doi: 10.1016/j.taap.2019.01.022.
Zheng Deng 1,  Fei Shi 1,  Zheng Zhou 2,  Feng Sun 3,  Meng-Hao Sun 3,  Qian Sun 2,  Lei Chen 1,  Deng Li 1,  Chen-Yi Jiang 1,  Rui-Zhe Zhao 1,  Di Cui 3,  Xing-Jie Wang 3,  Yi-Feng Jing 3,  Shu-Jie Xia 4,  Bang-Min Han 5
Affiliations

Affiliations

  • 1 Department of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China.
  • 2 Department of Urology, Shanghai General Hospital Affiliated to Nanjing Medical University, Shanghai 200080, China.
  • 3 Department of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China; Institute of Urology, Shanghai Jiao Tong University, Shanghai 200080, China.
  • 4 Department of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China; Institute of Urology, Shanghai Jiao Tong University, Shanghai 200080, China. Electronic address: xsjurologist@163.com.
  • 5 Department of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200080, China; Institute of Urology, Shanghai Jiao Tong University, Shanghai 200080, China. Electronic address: hanbm@163.com.
PMID: 30690042 DOI: 10.1016/j.taap.2019.01.022
Abstract

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.

Keywords

Benign prostatic hyperplasia; M1 macrophage; MAPK; ROS; Wound healing.

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