Elevated PTH induces endothelial to chondrogenic transition in aortic endothelial cells.
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Previous studies have shown that increased parathyroid hormone (PTH) due to secondary hyperparathyroidism in chronic kidney disease accelerates the arteriosclerotic fibrosis and calcification. Although the underlying mechanisms remain largely unknown, endothelial cells (ECs) have recently been demonstrated to participate in calcification in part by providing chondrogenic cells via the endothelial-to-mesenchymal transition (EndMT). Therefore, this study aimed to investigate whether elevated PTH could induce endothelial to chondrogenic transition in aortic ECs and to determine the possible underlying signaling pathway. We found that treatment of ECs with PTH significantly upregulated the expression of EndMT-related markers. Accordingly, ECs treated with PTH exhibited chondrogenic potential. In vivo, a lineage tracing model subjected mice with endothelial-specific GFP fluorescence to chronic PTH infusion showed a marked increase in the aortic expression of chondrocyte markers, and confocal microscopy revealed the endothelial origin of cells expressing chondrocyte markers in the aorta after PTH infusion. Furthermore, this in vitro study showed that PTH enhanced the nuclear localization of β-catenin in ECs, whereas, β-catenin siRNA or DKK1, an inhibitor of β-catenin nuclear translocation, attenuated the upregulation of EndMT-associated and chondrogenic markers induced by PTH. In summary, our study demonstrated that elevated PTH could induce the transition of ECs to chondrogenic cells via EndMT, possibly mediated by the nuclear translocation of β-catenin.
Published Version (Please cite this version)10.1152/ajprenal.00210.2016
Publication InfoCrowley, Steven Daniel; Liu, BC; Liu, H; Lv, LL; Ma, KL; Tang, RN; ... Zhang, Jian-Dong (2016). Elevated PTH induces endothelial to chondrogenic transition in aortic endothelial cells. Am J Physiol Renal Physiol. 10.1152/ajprenal.00210.2016. Retrieved from http://hdl.handle.net/10161/13062.
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Associate Professor of Medicine
Our laboratory explores the contribution of the immune system and inflammatory mediators to the progression of target organ damage in the setting of cardiovascular disease. We are pursuing several related projects in this field:(1) The actions of type 1 angiotensin receptors on specific immune cell populations in hypertension, target organ damage, and tissue fibrosis.(2) Cell-specific actions of inflammatory cytokines in regulating blood pressure and end-organ injury.(3) Mechan