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Tanshinone IIA Pretreatment Renders Free Flaps against Hypoxic Injury through Activating Wnt Signaling and Upregulating Stem Cell-Related Biomarkers
Partial or total flap necrosis after flap transplantation is sometimes clinically encountered in reconstructive surgery, often as a result of a period of hypoxia that exceeds the tolerance of the flap tissue. In this study, we determine whether tanshinone IIA (TSA) pretreatment can protect flap tiss...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4227206/ https://www.ncbi.nlm.nih.gov/pubmed/25302618 http://dx.doi.org/10.3390/ijms151018117 |
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author | Xu, Zihan Zhang, Zhenxin Wu, Lijun Sun, Yaowen Guo, Yadong Qin, Gaoping Mu, Shengzhi Fan, Ronghui Wang, Benfeng Gao, Wenjie |
author_facet | Xu, Zihan Zhang, Zhenxin Wu, Lijun Sun, Yaowen Guo, Yadong Qin, Gaoping Mu, Shengzhi Fan, Ronghui Wang, Benfeng Gao, Wenjie |
author_sort | Xu, Zihan |
collection | PubMed |
description | Partial or total flap necrosis after flap transplantation is sometimes clinically encountered in reconstructive surgery, often as a result of a period of hypoxia that exceeds the tolerance of the flap tissue. In this study, we determine whether tanshinone IIA (TSA) pretreatment can protect flap tissue against hypoxic injury and improve its viability. Primary epithelial cells isolated from the dorsal skin of mice were pretreated with TSA for two weeks. Cell counting kit-8 and Trypan Blue assays were carried out to examine the proliferation of TSA-pretreated cells after exposure to cobalt chloride. Then, Polymerase chain reaction and Western blot analysis were used to determine the expression of β-catenin, GSK-3β, SOX2, and OCT4 in TSA-treated cells. In vivo, after mice were pretreated with TSA for two weeks, a reproducible ischemic flap model was implemented, and the area of surviving tissue in the transplanted flaps was measured. Immunohistochemistry was also conducted to examine the related biomarkers mentioned above. Results show that epidermal cells, pretreated with TSA, showed enhanced resistance to hypoxia. Activation of the Wnt signaling pathway in TSA-pretreated cells was characterized by the upregulation of β-catenin and the downregulation of GSK-3β. The expression of SOX2 and OCT4 controlled by Wnt signaling were also found higher in TSA pretreated epithelial cells. In the reproducible ischaemic flap model, pretreatment with TSA enhanced resistance to hypoxia and increased the area of surviving tissue in transplanted flaps. The expression of Wnt signaling pathway components, stem-cell related biomarkers, and CD34, which are involved in the regeneration of blood vessels, was also upregulated in TSA-pretreated flap tissue. The results show that TSA pretreatment protects free flaps against hypoxic injury and increases the area of surviving tissue by activating Wnt signaling and upregulating stem cell-related biomarkers. |
format | Online Article Text |
id | pubmed-4227206 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-42272062014-11-12 Tanshinone IIA Pretreatment Renders Free Flaps against Hypoxic Injury through Activating Wnt Signaling and Upregulating Stem Cell-Related Biomarkers Xu, Zihan Zhang, Zhenxin Wu, Lijun Sun, Yaowen Guo, Yadong Qin, Gaoping Mu, Shengzhi Fan, Ronghui Wang, Benfeng Gao, Wenjie Int J Mol Sci Article Partial or total flap necrosis after flap transplantation is sometimes clinically encountered in reconstructive surgery, often as a result of a period of hypoxia that exceeds the tolerance of the flap tissue. In this study, we determine whether tanshinone IIA (TSA) pretreatment can protect flap tissue against hypoxic injury and improve its viability. Primary epithelial cells isolated from the dorsal skin of mice were pretreated with TSA for two weeks. Cell counting kit-8 and Trypan Blue assays were carried out to examine the proliferation of TSA-pretreated cells after exposure to cobalt chloride. Then, Polymerase chain reaction and Western blot analysis were used to determine the expression of β-catenin, GSK-3β, SOX2, and OCT4 in TSA-treated cells. In vivo, after mice were pretreated with TSA for two weeks, a reproducible ischemic flap model was implemented, and the area of surviving tissue in the transplanted flaps was measured. Immunohistochemistry was also conducted to examine the related biomarkers mentioned above. Results show that epidermal cells, pretreated with TSA, showed enhanced resistance to hypoxia. Activation of the Wnt signaling pathway in TSA-pretreated cells was characterized by the upregulation of β-catenin and the downregulation of GSK-3β. The expression of SOX2 and OCT4 controlled by Wnt signaling were also found higher in TSA pretreated epithelial cells. In the reproducible ischaemic flap model, pretreatment with TSA enhanced resistance to hypoxia and increased the area of surviving tissue in transplanted flaps. The expression of Wnt signaling pathway components, stem-cell related biomarkers, and CD34, which are involved in the regeneration of blood vessels, was also upregulated in TSA-pretreated flap tissue. The results show that TSA pretreatment protects free flaps against hypoxic injury and increases the area of surviving tissue by activating Wnt signaling and upregulating stem cell-related biomarkers. MDPI 2014-10-09 /pmc/articles/PMC4227206/ /pubmed/25302618 http://dx.doi.org/10.3390/ijms151018117 Text en © 2014 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Xu, Zihan Zhang, Zhenxin Wu, Lijun Sun, Yaowen Guo, Yadong Qin, Gaoping Mu, Shengzhi Fan, Ronghui Wang, Benfeng Gao, Wenjie Tanshinone IIA Pretreatment Renders Free Flaps against Hypoxic Injury through Activating Wnt Signaling and Upregulating Stem Cell-Related Biomarkers |
title | Tanshinone IIA Pretreatment Renders Free Flaps against Hypoxic Injury through Activating Wnt Signaling and Upregulating Stem Cell-Related Biomarkers |
title_full | Tanshinone IIA Pretreatment Renders Free Flaps against Hypoxic Injury through Activating Wnt Signaling and Upregulating Stem Cell-Related Biomarkers |
title_fullStr | Tanshinone IIA Pretreatment Renders Free Flaps against Hypoxic Injury through Activating Wnt Signaling and Upregulating Stem Cell-Related Biomarkers |
title_full_unstemmed | Tanshinone IIA Pretreatment Renders Free Flaps against Hypoxic Injury through Activating Wnt Signaling and Upregulating Stem Cell-Related Biomarkers |
title_short | Tanshinone IIA Pretreatment Renders Free Flaps against Hypoxic Injury through Activating Wnt Signaling and Upregulating Stem Cell-Related Biomarkers |
title_sort | tanshinone iia pretreatment renders free flaps against hypoxic injury through activating wnt signaling and upregulating stem cell-related biomarkers |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4227206/ https://www.ncbi.nlm.nih.gov/pubmed/25302618 http://dx.doi.org/10.3390/ijms151018117 |
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