Parathyroid hormone–related protein protects renal tubuloepithelial cells from apoptosis by activating transcription factor Runx2
Runx2 is a key transcription factor in bone development regulating several processes, including osteoblast apoptosis. The antiapoptotic effects of parathyroid hormone (PTH) in osteoblasts depend on Runx2-mediated transcription of prosurvival genes. In the kidney, PTH-related protein (PTHrP) promotes...
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Veröffentlicht in: | Kidney international 2013-05, Vol.83 (5), p.825-834 |
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Sprache: | eng |
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Zusammenfassung: | Runx2 is a key transcription factor in bone development regulating several processes, including osteoblast apoptosis. The antiapoptotic effects of parathyroid hormone (PTH) in osteoblasts depend on Runx2-mediated transcription of prosurvival genes. In the kidney, PTH-related protein (PTHrP) promotes tubulointerstitial cell survival by activating the PTH/PTHrP type 1 receptor. We found that Runx2 is expressed in renal tubuloepithelial MCT and HK2 cell lines in vitro and in the mouse kidney tubuloepithelium in vivo. The 1–36 amino-acid fragment of PTHrP was found to increase the expression and nuclear translocation of Runx2 in both cell lines in a dose- and time-dependent manner. PTHrP(1–36) protected renal tubuloepithelial cells from folic acid toxicity and serum deprivation, an effect inhibited by a dominant-negative Runx2 construct or a Runx2 siRNA. Furthermore, PTHrP(1–36) upregulated the antiapoptotic proteins Bcl-2 and osteopontin, and these effects were abolished by Runx2 siRNA. Runx2, osteopontin, and Bcl-2 were increased in tubuloepithelial cells from transgenic mice with PTHrP overexpression and in wild-type mice with acute or chronic renal failure. Thus, PTHrP regulates renal tubuloepithelial cell survival via Runx2 in the mammalian kidney. |
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ISSN: | 0085-2538 1523-1755 |
DOI: | 10.1038/ki.2012.476 |