Cargando…

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

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 fibrob...

Descripción completa

Detalles Bibliográficos
Autores principales: Deng, Lulu, Li, Qin, Lin, Guixian, Huang, Dan, Zeng, Xuxin, Wang, Xinwei, Li, Ping, Jin, Xiaobao, Zhang, Haifeng, Li, Chunmei, Chen, Lixin, Wang, Liwei, Huang, Shulin, Shao, Hongwei, Xu, Bin, Mao, Jianwen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Ivyspring International Publisher 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4729769/
https://www.ncbi.nlm.nih.gov/pubmed/26877779
http://dx.doi.org/10.7150/thno.13907
_version_ 1782412290108162048
author Deng, Lulu
Li, Qin
Lin, Guixian
Huang, Dan
Zeng, Xuxin
Wang, Xinwei
Li, Ping
Jin, Xiaobao
Zhang, Haifeng
Li, Chunmei
Chen, Lixin
Wang, Liwei
Huang, Shulin
Shao, Hongwei
Xu, Bin
Mao, Jianwen
author_facet Deng, Lulu
Li, Qin
Lin, Guixian
Huang, Dan
Zeng, Xuxin
Wang, Xinwei
Li, Ping
Jin, Xiaobao
Zhang, Haifeng
Li, Chunmei
Chen, Lixin
Wang, Liwei
Huang, Shulin
Shao, Hongwei
Xu, Bin
Mao, Jianwen
author_sort Deng, Lulu
collection PubMed
description 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.
format Online
Article
Text
id pubmed-4729769
institution National Center for Biotechnology Information
language English
publishDate 2016
publisher Ivyspring International Publisher
record_format MEDLINE/PubMed
spelling pubmed-47297692016-02-12 P-glycoprotein Mediates Postoperative Peritoneal Adhesion Formation by Enhancing Phosphorylation of the Chloride Channel-3 Deng, Lulu Li, Qin Lin, Guixian Huang, Dan Zeng, Xuxin Wang, Xinwei Li, Ping Jin, Xiaobao Zhang, Haifeng Li, Chunmei Chen, Lixin Wang, Liwei Huang, Shulin Shao, Hongwei Xu, Bin Mao, Jianwen Theranostics Research Paper 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. Ivyspring International Publisher 2016-01-01 /pmc/articles/PMC4729769/ /pubmed/26877779 http://dx.doi.org/10.7150/thno.13907 Text en © Ivyspring International Publisher. Reproduction is permitted for personal, noncommercial use, provided that the article is in whole, unmodified, and properly cited. See http://ivyspring.com/terms for terms and conditions.
spellingShingle Research Paper
Deng, Lulu
Li, Qin
Lin, Guixian
Huang, Dan
Zeng, Xuxin
Wang, Xinwei
Li, Ping
Jin, Xiaobao
Zhang, Haifeng
Li, Chunmei
Chen, Lixin
Wang, Liwei
Huang, Shulin
Shao, Hongwei
Xu, Bin
Mao, Jianwen
P-glycoprotein Mediates Postoperative Peritoneal Adhesion Formation by Enhancing Phosphorylation of the Chloride Channel-3
title P-glycoprotein Mediates Postoperative Peritoneal Adhesion Formation by Enhancing Phosphorylation of the Chloride Channel-3
title_full P-glycoprotein Mediates Postoperative Peritoneal Adhesion Formation by Enhancing Phosphorylation of the Chloride Channel-3
title_fullStr P-glycoprotein Mediates Postoperative Peritoneal Adhesion Formation by Enhancing Phosphorylation of the Chloride Channel-3
title_full_unstemmed P-glycoprotein Mediates Postoperative Peritoneal Adhesion Formation by Enhancing Phosphorylation of the Chloride Channel-3
title_short P-glycoprotein Mediates Postoperative Peritoneal Adhesion Formation by Enhancing Phosphorylation of the Chloride Channel-3
title_sort p-glycoprotein mediates postoperative peritoneal adhesion formation by enhancing phosphorylation of the chloride channel-3
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4729769/
https://www.ncbi.nlm.nih.gov/pubmed/26877779
http://dx.doi.org/10.7150/thno.13907
work_keys_str_mv AT denglulu pglycoproteinmediatespostoperativeperitonealadhesionformationbyenhancingphosphorylationofthechloridechannel3
AT liqin pglycoproteinmediatespostoperativeperitonealadhesionformationbyenhancingphosphorylationofthechloridechannel3
AT linguixian pglycoproteinmediatespostoperativeperitonealadhesionformationbyenhancingphosphorylationofthechloridechannel3
AT huangdan pglycoproteinmediatespostoperativeperitonealadhesionformationbyenhancingphosphorylationofthechloridechannel3
AT zengxuxin pglycoproteinmediatespostoperativeperitonealadhesionformationbyenhancingphosphorylationofthechloridechannel3
AT wangxinwei pglycoproteinmediatespostoperativeperitonealadhesionformationbyenhancingphosphorylationofthechloridechannel3
AT liping pglycoproteinmediatespostoperativeperitonealadhesionformationbyenhancingphosphorylationofthechloridechannel3
AT jinxiaobao pglycoproteinmediatespostoperativeperitonealadhesionformationbyenhancingphosphorylationofthechloridechannel3
AT zhanghaifeng pglycoproteinmediatespostoperativeperitonealadhesionformationbyenhancingphosphorylationofthechloridechannel3
AT lichunmei pglycoproteinmediatespostoperativeperitonealadhesionformationbyenhancingphosphorylationofthechloridechannel3
AT chenlixin pglycoproteinmediatespostoperativeperitonealadhesionformationbyenhancingphosphorylationofthechloridechannel3
AT wangliwei pglycoproteinmediatespostoperativeperitonealadhesionformationbyenhancingphosphorylationofthechloridechannel3
AT huangshulin pglycoproteinmediatespostoperativeperitonealadhesionformationbyenhancingphosphorylationofthechloridechannel3
AT shaohongwei pglycoproteinmediatespostoperativeperitonealadhesionformationbyenhancingphosphorylationofthechloridechannel3
AT xubin pglycoproteinmediatespostoperativeperitonealadhesionformationbyenhancingphosphorylationofthechloridechannel3
AT maojianwen pglycoproteinmediatespostoperativeperitonealadhesionformationbyenhancingphosphorylationofthechloridechannel3