Theranostics 2016; 6(2):204-218. doi:10.7150/thno.13907

Research Paper

P-glycoprotein Mediates Postoperative Peritoneal Adhesion Formation by Enhancing Phosphorylation of the Chloride Channel-3

Lulu Deng1,#, Qin Li1,7,#, Guixian Lin1,#, Dan Huang1,#, Xuxin Zeng5, Xinwei Wang1, Ping Li3, Xiaobao Jin1, Haifeng Zhang6, Chunmei Li1, Lixin Chen4, Liwei Wang4, Shulin Huang2, Hongwei Shao2, Bin Xu1,2,✉, Jianwen Mao1,✉

1. Guangdong Provincial Key Laboratory of pharmaceutical Bioactive Substances and School of Basic Medicine, Guangdong Pharmaceutical University, Guangzhou 510006, China
2. Guangdong Province Key Laboratory for Biotechnology Drug Candidates and School of Biosciences and Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou 510006, China
3. The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou 510000, China
4. Department of Pharmacology and Department of Physiology, Medical College, Jinan University, Guangzhou 510632, China
5. School of Medicine, Foshan University, Foshan 528000, China
6. Department of Pathology, School of Medicine, Xi'an Jiaotong University, Xi'an 710061, China
7. The People's Hospital of Liupanshui City, Liupanshui 553001, China
#These authors contributed equally to this work

Abstract

P-glycoprotein (P-gp) is encoded by the multidrug resistance (MDR1) gene and is well studied as a multi-drug resistance transporter. Peritoneal adhesion formation following abdominal surgery remains an important clinical problem. Here, we found that P-gp was highly expressed in human adhesion fibroblasts and promoted peritoneal adhesion formation in a rodent model. Knockdown of P-gp expression by intraperitoneal injection of MDR1-targeted siRNA significantly reduced both the peritoneal adhesion development rate and adhesion grades. Additionally, we found that operative injury up-regulated P-gp expression in peritoneal fibroblasts through the TGF-β1/Smad signaling pathway and histone H3 acetylation. The overexpression of P-gp accelerated migration and proliferation of fibroblasts via volume-activated Cl- current and cell volume regulation by enhancing phosphorylation of the chloride channel-3. Therefore, P-gp plays a critical role in postoperative peritoneal adhesion formation and may be a valuable therapeutic target for preventing the formation of peritoneal adhesions.

Keywords: P-glycoprotein, Peritoneal Adhesions, Chloride Channel-3

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How to cite this article:
Deng L, Li Q, Lin G, Huang D, Zeng X, Wang X, Li P, Jin X, Zhang H, Li C, Chen L, Wang L, Huang S, Shao H, Xu B, Mao J. P-glycoprotein Mediates Postoperative Peritoneal Adhesion Formation by Enhancing Phosphorylation of the Chloride Channel-3. Theranostics 2016; 6(2):204-218. doi:10.7150/thno.13907. Available from http://www.thno.org/v06p0204.htm