Disclosure: None of the authors have any relationships with companies that may have a financial interest in the content of this manuscript or any other interest to disclose.
Original Research Article
Parathyroid hormone-related protein is a hypertrophy factor for human mesangial cells: Implications for diabetic nephropathy†
Article first published online: 23 JAN 2012
Copyright © 2011 Wiley Periodicals, Inc.
Journal of Cellular Physiology
Volume 227, Issue 5, pages 1980–1987, May 2012
How to Cite
Ortega, A., Romero, M., Izquierdo, A., Troyano, N., Arce, Y., Ardura, J. A., Arenas, M. I., Bover, J., Esbrit, P. and Bosch, R. J. (2012), Parathyroid hormone-related protein is a hypertrophy factor for human mesangial cells: Implications for diabetic nephropathy. J. Cell. Physiol., 227: 1980–1987. doi: 10.1002/jcp.22926
- Issue published online: 23 JAN 2012
- Article first published online: 23 JAN 2012
- Accepted manuscript online: 5 JUL 2011 10:29AM EST
- Manuscript Accepted: 27 JUN 2011
- Manuscript Received: 7 OCT 2010
- Ministerio de Educación y Cultura of Spain. Grant Numbers: SAF2002-04356-C03-01, SAF2002-04356-C03-02, SAF2002-04356-C03-03, SAF2006-08747
- Ministerio de Ciencia e Innovación. Grant Number: SAF2009-12009-C02-01
- The Spanish Society of Nephrology
- The Eugenio Rodríguez Pascual Foundation
- Instituto de Salud Carlos III. Grant Number: RETICEF RD06/0013/1002
Hypertrophy of human mesangial cells (HMC) is among the earliest characteristics in patients with diabetic nephropathy (DN). Recently, we observed the upregulation of parathyroid hormone (PTH)-related protein (PTHrP) in experimental DN, associated with renal hypertrophy. Herein, we first examined whether PTHrP was overexpressed in human DN, and next assessed the putative role of this protein on high glucose (HG)-induced HMC hypertrophy. As previously found in mice, kidneys from diabetic patients showed an increased tubular and glomerular immunostaining for PTHrP. In HMC, HG medium increased PTHrP protein expression associated with the development of hypertrophy as assessed by cell protein content. This effect was also induced by PTHrP(1–36). HG and PTHrP(1–36)-induced hypertrophy were associated with an increase in cyclin D1 and p27Kip1 protein expression, a decreased cyclin E expression, and the prevention of cyclin E/cdk2 complex activation. Both PTHrP neutralizing antiserum (α-PTHrP) and the PTH/PTHrP receptor antagonist (JB4250) were able to abolish HG induction of hypertrophy, the aforementioned changes in cell cycle proteins, and also TGF-β1 up-regulation. Moreover, the capability of both HG and PTHrP(1–36) to induce HMC hypertrophy was abolished by α-TGFβ1. These data show for the first time that PTHrP is upregulated in the kidney of patients with DN. Our findings also demonstrate that PTHrP acts as an important mediator of HG-induced HMC hypertrophy by modulating cell cycle regulatory proteins and TGF-β1. J. Cell. Physiol. 227: 1980–1987, 2012. © 2011 Wiley Periodicals, Inc.