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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...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Ivyspring International Publisher
2016
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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 |
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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 |
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