The Involvement of Notch1-RBP-Jk/Msx2 Signaling Pathway in Aortic Calcification of Diabetic Nephropathy Rats

Background. This study explored the changes in expression of vascular smooth muscle cell (VSMC) markers and osteogenic markers, as well as the involvement of Notch1-RBP-Jk/Msx2 pathway in a rat model of diabetic nephropathy (DN) with vascular calcification. Methods. A rat model of DN with concomitan...

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Main Authors: Caipan Gong, Li Li, Chunmei Qin, Weihua Wu, Qi Liu, Ying Li, Linwang Gan, Santao Ou
Format: Article
Language:English
Published: Wiley 2017-01-01
Series:Journal of Diabetes Research
Online Access:http://dx.doi.org/10.1155/2017/8968523
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author Caipan Gong
Li Li
Chunmei Qin
Weihua Wu
Qi Liu
Ying Li
Linwang Gan
Santao Ou
author_facet Caipan Gong
Li Li
Chunmei Qin
Weihua Wu
Qi Liu
Ying Li
Linwang Gan
Santao Ou
author_sort Caipan Gong
collection DOAJ
description Background. This study explored the changes in expression of vascular smooth muscle cell (VSMC) markers and osteogenic markers, as well as the involvement of Notch1-RBP-Jk/Msx2 pathway in a rat model of diabetic nephropathy (DN) with vascular calcification. Methods. A rat model of DN with concomitant vascular calcification was created by intraperitoneal injection of streptozotocin followed by administration of vitamin D3 and nicotine. Biochemical analysis and histological examination of aortic tissue were performed. VSMC markers and osteogenic markers as well as target molecules in Notch1-RBP-Jk/Msx2 were determined by quantitative real-time polymerase chain reaction and immunohistochemical analysis. Results. Serum calcium and phosphorus levels were significantly increased in model rats as compared to that in normal controls. Diabetic rats with vascular calcification exhibited mineral deposits in aortic intima-media accompanied by decreased expression of VSMC markers and increased expression of osteogenic markers. Notch1, RBP-Jk, Msx2, Jagged1, and N1-ICD were barely expressed in the aortic wall of normal rats. In contrast, these were significantly increased in the model group at all time points (8, 12, and 16 weeks), as compared to that in the normal rats. Conclusion. Activation of the Notch1-RBP-Jk/Msx2 signaling pathway may be involved in the development and progression of vascular calcification in DN.
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spelling doaj-art-bfab158b937847c689e0cf676349803e2025-02-03T01:27:52ZengWileyJournal of Diabetes Research2314-67452314-67532017-01-01201710.1155/2017/89685238968523The Involvement of Notch1-RBP-Jk/Msx2 Signaling Pathway in Aortic Calcification of Diabetic Nephropathy RatsCaipan Gong0Li Li1Chunmei Qin2Weihua Wu3Qi Liu4Ying Li5Linwang Gan6Santao Ou7Department of Nephrology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, ChinaDepartment of Nephrology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, ChinaDepartment of Nephrology, Luzhou People’s Hospital, Luzhou, Sichuan 646000, ChinaDepartment of Nephrology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, ChinaDepartment of Nephrology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, ChinaDepartment of Nephrology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, ChinaDepartment of Nephrology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, ChinaDepartment of Nephrology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, ChinaBackground. This study explored the changes in expression of vascular smooth muscle cell (VSMC) markers and osteogenic markers, as well as the involvement of Notch1-RBP-Jk/Msx2 pathway in a rat model of diabetic nephropathy (DN) with vascular calcification. Methods. A rat model of DN with concomitant vascular calcification was created by intraperitoneal injection of streptozotocin followed by administration of vitamin D3 and nicotine. Biochemical analysis and histological examination of aortic tissue were performed. VSMC markers and osteogenic markers as well as target molecules in Notch1-RBP-Jk/Msx2 were determined by quantitative real-time polymerase chain reaction and immunohistochemical analysis. Results. Serum calcium and phosphorus levels were significantly increased in model rats as compared to that in normal controls. Diabetic rats with vascular calcification exhibited mineral deposits in aortic intima-media accompanied by decreased expression of VSMC markers and increased expression of osteogenic markers. Notch1, RBP-Jk, Msx2, Jagged1, and N1-ICD were barely expressed in the aortic wall of normal rats. In contrast, these were significantly increased in the model group at all time points (8, 12, and 16 weeks), as compared to that in the normal rats. Conclusion. Activation of the Notch1-RBP-Jk/Msx2 signaling pathway may be involved in the development and progression of vascular calcification in DN.http://dx.doi.org/10.1155/2017/8968523
spellingShingle Caipan Gong
Li Li
Chunmei Qin
Weihua Wu
Qi Liu
Ying Li
Linwang Gan
Santao Ou
The Involvement of Notch1-RBP-Jk/Msx2 Signaling Pathway in Aortic Calcification of Diabetic Nephropathy Rats
Journal of Diabetes Research
title The Involvement of Notch1-RBP-Jk/Msx2 Signaling Pathway in Aortic Calcification of Diabetic Nephropathy Rats
title_full The Involvement of Notch1-RBP-Jk/Msx2 Signaling Pathway in Aortic Calcification of Diabetic Nephropathy Rats
title_fullStr The Involvement of Notch1-RBP-Jk/Msx2 Signaling Pathway in Aortic Calcification of Diabetic Nephropathy Rats
title_full_unstemmed The Involvement of Notch1-RBP-Jk/Msx2 Signaling Pathway in Aortic Calcification of Diabetic Nephropathy Rats
title_short The Involvement of Notch1-RBP-Jk/Msx2 Signaling Pathway in Aortic Calcification of Diabetic Nephropathy Rats
title_sort involvement of notch1 rbp jk msx2 signaling pathway in aortic calcification of diabetic nephropathy rats
url http://dx.doi.org/10.1155/2017/8968523
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