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The Involvement of Notch1-RBP-Jk/Msx2 Signaling Pathway in Aortic Calcification of Diabetic Nephropathy Rats
Caipan Gong1, Li Li1, Chunmei Qin2
1Department of Nephrology, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646000, China.
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.
Insights
Diabetic nephropathy with vascular calcification involves changes in smooth muscle and bone cell markers. The Notch1-RBP-Jk/Msx2 pathway activation appears to drive this vascular calcification progression.
Area of Science:
- Nephrology
- Cardiovascular Biology
- Molecular Biology
Background:
- Diabetic nephropathy (DN) is associated with vascular calcification.
- Vascular calcification in DN involves alterations in vascular smooth muscle cell (VSMC) and osteogenic markers.
- The role of the Notch1-RBP-Jk/Msx2 pathway in DN-related vascular calcification requires further investigation.
Purpose of the Study:
- To investigate changes in VSMC and osteogenic markers in a rat model of DN with vascular calcification.
- To explore the involvement of the Notch1-RBP-Jk/Msx2 signaling pathway in this condition.
Main Methods:
- A rat model of diabetic nephropathy with vascular calcification was established using streptozotocin, vitamin D3, and nicotine.
- Aortic tissue was analyzed for biochemical and histological changes.
- Quantitative real-time polymerase chain reaction and immunohistochemical analysis were used to assess marker expression.
Main Results:
- Model rats showed elevated serum calcium and phosphorus levels.
- Aortic intima-media displayed mineral deposits, reduced VSMC markers, and increased osteogenic markers.
- Expression of Notch1, RBP-Jk, Msx2, Jagged1, and N1-ICD significantly increased in model rats compared to controls.
Conclusions:
- The Notch1-RBP-Jk/Msx2 signaling pathway is implicated in the development and progression of vascular calcification in diabetic nephropathy.
- These findings highlight a potential therapeutic target for managing vascular complications in DN.
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