Related Experiment Video
Updated: Dec 5, 2025
Isolation of Primary Patient-specific Aortic Smooth Muscle Cells and Semiquantitative Real-time Contraction Measurements In Vitro
Published on: February 15, 2022
Polycystin-1 Downregulation Induced Vascular Smooth Muscle Cells Phenotypic Alteration and Extracellular Matrix
Jing Zhang1, Fei Liu2, Yu-Bin He1,3
1Department of Cardiovascular Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.
Insights
Polycystin-1 (PC-1) downregulation in thoracic aortic dissection (TAD) alters vascular smooth muscle cell (VSMC) phenotypes and extracellular matrix (ECM) remodeling via the mTOR/S6K/S6 pathway. Rapamycin may inhibit TAD progression.
Area of Science:
- Cardiovascular Biology
- Molecular Medicine
- Vascular Cell Biology
Background:
- Polycystin-1 (PC-1), encoded by the polycystic kidney disease-1 (PKD-1) gene, plays a role in cellular functions.
- Thoracic aortic dissection (TAD) involves significant changes in aortic vascular smooth muscle cells (VSMCs) and extracellular matrix (ECM).
Purpose of the Study:
- To investigate the regulatory mechanisms of PC-1 on VSMC phenotypes and ECM function in TAD.
- To elucidate the role of PC-1 in the pathogenesis of TAD.
Main Methods:
- Analysis of aortic tissues and primary VSMCs from TAD patients and controls.
- Immunohistochemistry, immunofluorescence, immunocytochemistry, Western blot, and RT-qPCR were employed.
- Lentivirus-mediated downregulation or overexpression of PC-1 in VSMCs.
Main Results:
- PC-1 and VSMC contractile markers were decreased, while synthetic markers, MMP-2, collagen I, and collagen III were increased in TAD.
- PC-1 downregulation promoted VSMC synthetic phenotypes and ECM remodeling, activating the mTOR/S6K/S6 pathway.
- PC-1 upregulation reversed these effects, and rapamycin inhibited the changes induced by PC-1 downregulation.
Conclusions:
- PC-1 downregulation drives VSMC phenotypic alteration and ECM remodeling through mTOR/S6K/S6 pathway activation in TAD.
- PC-1 downregulation is a potential mechanism in TAD development and progression.
- Rapamycin shows potential as an inhibitor to attenuate TAD development and progression.
Objective:
Polycystin-1 (PC-1) is a protein encoded by the gene of polycystic kidney disease-1 (PKD-1). This study was designed to investigate the regulatory mechanisms of PC-1 on phenotypes of aortic vascular smooth muscle cells (VSMCs) and functions of extracellular matrix (ECM) in thoracic aortic dissection (TAD).
Methods:
Aortic tissues from patients with TAD and healthy controls were collected, primary aortic VSMCs were also isolated. Immunohistochemistry, immunofluorescence, and immunocytochemistry was used to visualize the target proteins. Western blot and RT-qPCR were used to examine the expression of mRNA and proteins. Lentivirus infection was used to downregulate or overexpress PC-1.
Results:
Compared with the control group, expression of PC-1 and the contractile phenotypic markers of VSMCs were decreased in TAD group, whereas expression of the synthetic markers of VSMCs, matrix metalloproteinase (MMP)-2, collagen I and collagen III were increased. The phosphorylation of mTOR, S6K and S6 were also elevated in TAD group. PC-1 downregulation of aortic VSMCs inhibited the expression of the contractile markers, but elevated the expression of the synthetic markers, MMP-2, collagen I and collagen III compared with the control group. The phosphorylation of mTOR, S6K and S6 were also increased in PKD-1-knockdown VSMCs. PC-1 upregulation reversed all these expression characteristics in aortic VSMCs. Furthermore, rapamycin treatment to PKD-1-knockdown VSMCs inhibited the effects caused by PC-1 downregulation.
Conclusion:
Our study revealed PC-1 downregulation induces aortic VSMCs phenotypic alteration and ECM remodeling via activation of mTOR/S6K/S6 signaling pathway. Downregulation of PC-1 might be a potential mechanism for the development and progression of TAD. Rapamycin might be a potential inhibitor to attenuate the development and progression of TAD.
More Related Videos
06:14Murine Aortic Crush Injury: An Efficient In Vivo Model of Smooth Muscle Cell Proliferation and Endothelial Function
Published on: June 11, 2017
05:31Murine Model of Thoracic Aortic Dissection Induced by Oral β-Aminopropionitrile and Subcutaneous Angiotensin II Infusion
Published on: May 16, 2025
