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J Cell Biochem. 2014 Oct;115(10):1692-701. doi: 10.1002/jcb.24832.

Nuclear translocation of β-catenin mediates the parathyroid hormone-induced endothelial-to-mesenchymal transition in human renal glomerular endothelial cells.

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  • 1Institute of Nephrology, Zhongda Hospital, Southeast University School of Medicine, Nanjing, China.

Abstract

Emerging evidence shows that increased parathyroid hormone (PTH) accelerates endothelial injury and subsequent organ fibrosis. Although the underlying mechanisms remain largely unknown, the endothelial-to-mesenchymal transition (EndMT) has recently been demonstrated to be a crucial event during fibrotic disorders. Therefore, the present study aimed to investigate whether elevated PTH could induce EndMT in primary human renal glomerular endothelial cells (GECs) and to determine the possible underlying signaling pathway. The expression of EndMT-related markers was determined by real-time PCR, Western blotting, and confocal microscopy. The results showed that PTH receptor (PTHR) was expressed in GECs and its expression was decreased by increasing concentration of PTH. Moreover, PTH significantly inhibited the expression of endothelial marker CD31 and increased the expression of mesenchymal markers FSP1 and α-SMA in concentration- and time-dependent manners. Confocal microscopy revealed an increasing overlap of CD31 with FSP1 in some GECs after PTH treatment. The expression of type I collagen was upregulated by PTH. Furthermore, PTH enhanced the nuclear β-catenin protein levels, and decreased cytoplasmic β-catenin expression in GECs was observed. In contrast, DKK1, an inhibitor of β-catenin nuclear translocation, attenuated such changes in EndMT-related markers induced by PTH. In summary, these data demonstrated that elevated PTH-induced EndMT in human GECs might be partially mediated by the nuclear translocation of β-catenin.

© 2014 Wiley Periodicals, Inc.

KEYWORDS:

DKK1; ENDOTHELIAL-TO-MESENCHYMAL TRANSITION; GLOMERULAR ENDOTHELIAL CELL; PARATHYROID HORMONE; β-CATENIN

PMID:
24821601
[PubMed - indexed for MEDLINE]
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