Cargando…

High glucose mediates endothelial-to-chondrocyte transition in human aortic endothelial cells

BACKGROUND: Vascular calcification is one of the common complications in diabetes mellitus. Many studies have shown that high glucose (HG) caused cardiovascular calcification, but its underlying mechanism is not fully understood. Recently, medial calcification has been most commonly described in the...

Descripción completa

Detalles Bibliográficos
Autores principales: Tang, Rining, Gao, Min, Wu, Min, Liu, Hong, Zhang, Xiaoliang, Liu, Bicheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3502155/
https://www.ncbi.nlm.nih.gov/pubmed/22998723
http://dx.doi.org/10.1186/1475-2840-11-113
_version_ 1782250278068682752
author Tang, Rining
Gao, Min
Wu, Min
Liu, Hong
Zhang, Xiaoliang
Liu, Bicheng
author_facet Tang, Rining
Gao, Min
Wu, Min
Liu, Hong
Zhang, Xiaoliang
Liu, Bicheng
author_sort Tang, Rining
collection PubMed
description BACKGROUND: Vascular calcification is one of the common complications in diabetes mellitus. Many studies have shown that high glucose (HG) caused cardiovascular calcification, but its underlying mechanism is not fully understood. Recently, medial calcification has been most commonly described in the vessels of patients with diabetes. Chondrocytes were involved in the medial calcification. Recent studies have shown that the conversion into mesenchymal stem cells (MSCs) via the endothelial-to-mesenchymal transition (EndMT) could be triggered in chondrocytes. Our previous research has indicated that HG induced EndMT in human aortic endothelial cells (HAECs). Therefore, we addressed the question of whether HG-induced EndMT could be transitioned into MSCs and differentiated into chondrocytes. METHODS: HAECs were divided into three groups: a normal glucose (NG) group, HG group (30 mmol/L), and mannitol (5.5 mmol/L NG + 24.5 mmol/L) group. Pathological changes were investigated using fluorescence microscopy and electron microscopy. Immunofluorescence staining was performed to detect the co-expression of endothelial markers, such as CD31, and fibroblast markers, such as fibroblast-specific protein 1 (FSP-1). The expression of FSP-1 was detected by real time-PCR and western blots. Endothelial-derived MSCs were grown in MSC medium for one week. The expression of the MSCs markers STRO-1, CD44, CD10 and the chondrocyte marker SOX9 was detected by immunofluorescence staining and western blots. Chondrocyte expression was detected by alcian blue staining. Calcium deposits were analyzed by alizarin red staining. RESULTS: The incubation of HAECs exposed to HG resulted in a fibroblast-like phenotype. Double staining of the HAECs indicated a co-localization of CD31 and FSP-1. The expression of FSP-1 was significantly increased in the HG group, and the cells undergoing EndMT also expressed STRO-1, CD44 and SOX9 compared with the controls (P < 0.05). Additionally, alcian blue staining in the HG group was positive compared to the NG group. Consistent with the evaluation of SOX9 expression, calcium deposits analyzed by alizarin red staining were also enhanced by the HG treatment. Specifically, we showed that HG-induced EndMT is accompanied by the activation of the canonical Snail pathway. CONCLUSIONS: Our study demonstrated that HG could induce endothelial cells transdifferentiation into chondrocyte-like cells via the EndMT, which is mediated in part by the activation of the Snail signaling pathway.
format Online
Article
Text
id pubmed-3502155
institution National Center for Biotechnology Information
language English
publishDate 2012
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-35021552012-11-21 High glucose mediates endothelial-to-chondrocyte transition in human aortic endothelial cells Tang, Rining Gao, Min Wu, Min Liu, Hong Zhang, Xiaoliang Liu, Bicheng Cardiovasc Diabetol Original Investigation BACKGROUND: Vascular calcification is one of the common complications in diabetes mellitus. Many studies have shown that high glucose (HG) caused cardiovascular calcification, but its underlying mechanism is not fully understood. Recently, medial calcification has been most commonly described in the vessels of patients with diabetes. Chondrocytes were involved in the medial calcification. Recent studies have shown that the conversion into mesenchymal stem cells (MSCs) via the endothelial-to-mesenchymal transition (EndMT) could be triggered in chondrocytes. Our previous research has indicated that HG induced EndMT in human aortic endothelial cells (HAECs). Therefore, we addressed the question of whether HG-induced EndMT could be transitioned into MSCs and differentiated into chondrocytes. METHODS: HAECs were divided into three groups: a normal glucose (NG) group, HG group (30 mmol/L), and mannitol (5.5 mmol/L NG + 24.5 mmol/L) group. Pathological changes were investigated using fluorescence microscopy and electron microscopy. Immunofluorescence staining was performed to detect the co-expression of endothelial markers, such as CD31, and fibroblast markers, such as fibroblast-specific protein 1 (FSP-1). The expression of FSP-1 was detected by real time-PCR and western blots. Endothelial-derived MSCs were grown in MSC medium for one week. The expression of the MSCs markers STRO-1, CD44, CD10 and the chondrocyte marker SOX9 was detected by immunofluorescence staining and western blots. Chondrocyte expression was detected by alcian blue staining. Calcium deposits were analyzed by alizarin red staining. RESULTS: The incubation of HAECs exposed to HG resulted in a fibroblast-like phenotype. Double staining of the HAECs indicated a co-localization of CD31 and FSP-1. The expression of FSP-1 was significantly increased in the HG group, and the cells undergoing EndMT also expressed STRO-1, CD44 and SOX9 compared with the controls (P < 0.05). Additionally, alcian blue staining in the HG group was positive compared to the NG group. Consistent with the evaluation of SOX9 expression, calcium deposits analyzed by alizarin red staining were also enhanced by the HG treatment. Specifically, we showed that HG-induced EndMT is accompanied by the activation of the canonical Snail pathway. CONCLUSIONS: Our study demonstrated that HG could induce endothelial cells transdifferentiation into chondrocyte-like cells via the EndMT, which is mediated in part by the activation of the Snail signaling pathway. BioMed Central 2012-09-22 /pmc/articles/PMC3502155/ /pubmed/22998723 http://dx.doi.org/10.1186/1475-2840-11-113 Text en Copyright ©2012 Tang et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Investigation
Tang, Rining
Gao, Min
Wu, Min
Liu, Hong
Zhang, Xiaoliang
Liu, Bicheng
High glucose mediates endothelial-to-chondrocyte transition in human aortic endothelial cells
title High glucose mediates endothelial-to-chondrocyte transition in human aortic endothelial cells
title_full High glucose mediates endothelial-to-chondrocyte transition in human aortic endothelial cells
title_fullStr High glucose mediates endothelial-to-chondrocyte transition in human aortic endothelial cells
title_full_unstemmed High glucose mediates endothelial-to-chondrocyte transition in human aortic endothelial cells
title_short High glucose mediates endothelial-to-chondrocyte transition in human aortic endothelial cells
title_sort high glucose mediates endothelial-to-chondrocyte transition in human aortic endothelial cells
topic Original Investigation
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3502155/
https://www.ncbi.nlm.nih.gov/pubmed/22998723
http://dx.doi.org/10.1186/1475-2840-11-113
work_keys_str_mv AT tangrining highglucosemediatesendothelialtochondrocytetransitioninhumanaorticendothelialcells
AT gaomin highglucosemediatesendothelialtochondrocytetransitioninhumanaorticendothelialcells
AT wumin highglucosemediatesendothelialtochondrocytetransitioninhumanaorticendothelialcells
AT liuhong highglucosemediatesendothelialtochondrocytetransitioninhumanaorticendothelialcells
AT zhangxiaoliang highglucosemediatesendothelialtochondrocytetransitioninhumanaorticendothelialcells
AT liubicheng highglucosemediatesendothelialtochondrocytetransitioninhumanaorticendothelialcells