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| Status |
Public on Dec 31, 2023 |
| Title |
Stanniocalcin-1 mediates aortic valve calcification via promoting osteochondrogenic differentiation from valve interstitial cells |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Although calcific aortic valve stenosis (CAVS) is the most prevalent valvular heart disease, the molecular mechanisms underlying aortic valve calcification remain unknown. Here, we found a significant elevation in stanniocalcin-1 (STC1) expression in the valve interstitial cells (VICs) of calcific aortic valves by combined analysis of our comprehensive gene expression data and microarray datasets reported previously. Immunohistochemical staining showed that STC1 was located around the calcific area in the aortic valves of patients with CAVS. In vitro experiments using inhibitors and siRNA targeting osteoblast differentiation signaling revealed that activation of the Akt/STC1 axis was essential for runt-related transcription factor 2 (RUNX2) induction in the VICs. RNA sequencing and bioinformatics analysis of STC1-knocked down VICs in osteoblast differentiation medium resulted in silencing of the induction of osteoarthritis signaling-related genes, including RUNX2 and COL10A1. STC1 depletion in the murine CAVS model improved aortic valve dysfunction with high peak velocity and valve thickening and suppressed the appearance of osteochondrocytes. STC1-deficient mice also exhibited complete calcification abolishment, although partial valve thickening by aortic valve injury was observed. Our findings suggest that STC1 may be a critical factor in determining valve calcification and a novel target for preventing the transition to severe CAVS with calcification.
We analyzed the gene expression profiles of the valve interstitial cells (VICs) isolated from noncalcific and calcific areas in calcific aortic valve stenosis (CAVS) donors using a gene microarray.
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| Overall design |
We compared the gene expression profiles of the valve interstitial cells (VICs) isolated from noncalcific and calcific areas in three calcific aortic valve stenosis (CAVS) donors with calcification.
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| Contributor(s) |
Nakashiro K |
| Citation missing |
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| Submission date |
Mar 07, 2023 |
| Last update date |
Jan 01, 2024 |
| Contact name |
Koh-ichi Nakashiro |
| E-mail(s) |
nakako@m.ehime-u.ac.jp
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| Phone |
+81899605393
|
| Organization name |
Ehime University Graduate School of Medicine
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| Department |
Oral and Maxillofacial Surgery
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| Street address |
454 Shitsukawa
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| City |
Toon |
| State/province |
Ehime |
| ZIP/Postal code |
791-0295 |
| Country |
Japan |
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| Platforms (1) |
| GPL13667 |
[HG-U219] Affymetrix Human Genome U219 Array |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA941792 |
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