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DOI: 10.1055/s-0030-1268955
The MSX1 gene as downstream target of transforming growth factor beta1: Impact in human aortic valve calcification
Recent data from our group has shown enhancement of the MSX1 gene expression as well as valvular interstitial cell (VIC) calcification on exposure to transforming growth factor beta1 (TGF-β1). The MSX1 gene has been shown to induce osteoprogenitor cell proliferation under the control of TGF-beta in mandible bone formation. Based on these rationales we sought to investigate the expression profile of MSX1 in isolated human VIC stimulated with TGF-β1, and in calcified human aortic valve leaflets.
Human aortic VIC were exposed to TGF-β1 for 21 days. Real time PCR (RT PCR) Array, Western blot analysis, alkaline phosphatase staining, alizarin red S staining, histochemical staining, and apoptosis measurement were performed after treatment. Protein and RNA was extracted from calcified human aortic valve leaflets and similar evaluations carried out.
Calcific nodule formation was demonstrated in VIC cultures exposed to TGF-β1. (P<0.05), in contrast to unstimulated cultures. RT PCR Array demonstrated a significant (P<0.05) upregulation of the MSX1 gene in TGF-β1 treated cells when compared to untreated cultures. Apoptosis analysis showed that apoptotic cells were concentrated in the calcific nodules. There was a corresponding increase in MSX1 gene expression in calcified human aortic valve leaflets as shown by RT PCR Array and westernblot analysis.
TGF-β1 enhances the expression of MSX1 in calcific aortic valve interstitial cells.. Thus MSX1 may regulate the degeneration of VIC in calcific aortic stenosis. Understanding the downstream signalling pathways of TGF-β1 will support a therapeutic direction for the pharmacotherapy of aortic valve disease.