title: P-glycoprotein Mediates Postoperative Peritoneal Adhesion Formation by Enhancing Phosphorylation of the Chloride Channel-3.
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.
authors.affiliation: 1. Guangdong Provincial Key Laboratory of pharmaceutical Bioactive Substances and School of Basic Medicine, Guangdong Pharmaceutical University, Guangzhou 510006, China.
authors.forename: Lulu
authors.initials: L
authors.lastname: Deng
authors.affiliation: 1. Guangdong Provincial Key Laboratory of pharmaceutical Bioactive Substances and School of Basic Medicine, Guangdong Pharmaceutical University, Guangzhou 510006, China; 7. The People's Hospital of Liupanshui City, Liupanshui 553001, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Li
authors.affiliation: 1. Guangdong Provincial Key Laboratory of pharmaceutical Bioactive Substances and School of Basic Medicine, Guangdong Pharmaceutical University, Guangzhou 510006, China.
authors.forename: Guixian
authors.initials: G
authors.lastname: Lin
authors.affiliation: 1. Guangdong Provincial Key Laboratory of pharmaceutical Bioactive Substances and School of Basic Medicine, Guangdong Pharmaceutical University, Guangzhou 510006, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Huang
authors.affiliation: 5. School of Medicine, Foshan University, Foshan 528000, China.
authors.forename: Xuxin
authors.initials: X
authors.lastname: Zeng
authors.affiliation: 1. Guangdong Provincial Key Laboratory of pharmaceutical Bioactive Substances and School of Basic Medicine, Guangdong Pharmaceutical University, Guangzhou 510006, China.
authors.forename: Xinwei
authors.initials: X
authors.lastname: Wang
authors.affiliation: 3. The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou 510000, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.affiliation: 1. Guangdong Provincial Key Laboratory of pharmaceutical Bioactive Substances and School of Basic Medicine, Guangdong Pharmaceutical University, Guangzhou 510006, China.
authors.forename: Xiaobao
authors.initials: X
authors.lastname: Jin
authors.affiliation: 6. Department of Pathology, School of Medicine, Xi'an Jiaotong University, Xi'an 710061, China.
authors.forename: Haifeng
authors.initials: H
authors.lastname: Zhang
authors.affiliation: 1. Guangdong Provincial Key Laboratory of pharmaceutical Bioactive Substances and School of Basic Medicine, Guangdong Pharmaceutical University, Guangzhou 510006, China.
authors.forename: Chunmei
authors.initials: C
authors.lastname: Li
authors.affiliation: 4. Department of Pharmacology and Department of Physiology, Medical College, Jinan University, Guangzhou 510632, China.
authors.forename: Lixin
authors.initials: L
authors.lastname: Chen
authors.affiliation: 4. Department of Pharmacology and Department of Physiology, Medical College, Jinan University, Guangzhou 510632, China.
authors.forename: Liwei
authors.initials: L
authors.lastname: Wang
authors.affiliation: 2. Guangdong Province Key Laboratory for Biotechnology Drug Candidates and School of Biosciences and Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou 510006, China.
authors.forename: Shulin
authors.initials: S
authors.lastname: Huang
authors.affiliation: 2. Guangdong Province Key Laboratory for Biotechnology Drug Candidates and School of Biosciences and Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou 510006, China.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Shao
authors.affiliation: 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.
authors.forename: Bin
authors.initials: B
authors.lastname: Xu
authors.affiliation: 1. Guangdong Provincial Key Laboratory of pharmaceutical Bioactive Substances and School of Basic Medicine, Guangdong Pharmaceutical University, Guangzhou 510006, China.
authors.forename: Jianwen
authors.initials: J
authors.lastname: Mao
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D018118:Chloride Channels / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism; D020868:Gene Silencing; D006801:Humans; D007813:Laparotomy / Q000009:adverse effects; D010532:Peritoneal Diseases / Q000209:etiology / Q000378:metabolism*; D010766:Phosphorylation; D011183:Postoperative Complications / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D051381:Rats; D015854:Up-Regulation
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D018118:Chloride Channels
keywords: Chloride Channel-3; P-glycoprotein; Peritoneal Adhesions