Yet more evidence of the importance of T3...
Am J Transl Res. 2016; 8(11): 4694–4704.
Published online 2016 Nov 15.
T3 inhibits the calcification of vascular smooth muscle cells and the potential mechanism
Xiaodan Chang,1,2,* Baohong Zhang,3,* Li Lihua,4 and Zhichun Feng1
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Objective: This study aimed to investigate the potential molecular mechanism underlying the T3 induced vascular calcification and phenotype transformation of vascular smooth muscle cells (VSMCs). Methods: Rat thoracic aortic smooth muscle cells (A7r5) were cultured in vitro and randomly assigned into normal control group, calcification group, T3 group and inhibitor group. Results: When compared with normal control group, the osteocalcin content, ALP activity, Osterix and Runx2 mRNA expression and OPN protein expression increased significantly (P<0.01), and the protein expression of SMα and SM22α reduced dramatically in A7r5 cells of calcification group (P<0.01). After T3 treatment, the osteocalcin content and ALP activity reduced markedly, mRNA expression of Osterix and Runx2 and OPN protein expression reduced significantly. However, MMI (inhibitor of T3) was able to block the above effects of T3. When compared with calcification group, Osterix and Runx2 mRNA expression and OPN protein expression increased markedly (P<0.01). In addition, the protein expression of ERK1/2, p-ERK, Akt and p-Akt increased significantly in calcification group. In the presence of integrin αvβ3/ERK blocker (PD98059) and/or PI3K/Akt antagonist (LY294002), T3 was still able to inhibit the calcification, and this effect was similar to that after treatment with inhibitors alone. Moreover, LY294002 had a better inhibitory effect as compared to PD98059.
Conclusion: T3 may act on PI3K/Akt signaling pathway to inhibit the phenotype transformation of VSMC, which then suppresses the calcium/phosphate induced calcification of rat VSMCs. Thus, T3 is an endogenous molecule that can protect the blood vessels against calcification.
Keywords: Thyroid hormone, vascular calcification, vascular smooth muscle cells, phenotype switch, signaling pathway
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