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

نویسندگان

  • Lulu Deng
  • Qin Li
  • Guixian Lin
  • Dan Huang
  • Xuxin Zeng
  • Xinwei Wang
  • Ping Li
  • Xiaobao Jin
  • Haifeng Zhang
  • Chunmei Li
  • Lixin Chen
  • Liwei Wang
  • Shulin Huang
  • Hongwei Shao
  • Bin Xu
  • Jianwen Mao
چکیده

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.

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عنوان ژورنال:

دوره 6  شماره 

صفحات  -

تاریخ انتشار 2016