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Kidney Int. 2016 Apr;89(4):848-61. doi: 10.1016/j.kint.2015.12.037. Epub 2016 Feb 18.

The role of PDGF-D in healthy and fibrotic kidneys.

Author information

1
Division of Nephrology, RWTH University of Aachen, Aachen, Germany; Institute of Pathology, RWTH University of Aachen, Aachen, Germany.
2
Institute of Pathology, RWTH University of Aachen, Aachen, Germany.
3
Division of Nephrology, RWTH University of Aachen, Aachen, Germany; Institute of Pathology, RWTH University of Aachen, Aachen, Germany; Institute of Molecular Biomedicine, Comenius University, Bratislava, Slovakia.
4
Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
5
Institute of Molecular Pathobiochemistry, Experimental Gene Therapy and Clinical Chemistry, RWTH University of Aachen, Aachen, Germany.
6
Department of Pathology, University of Washington, Seattle, WA, USA.
7
Division of Nephrology, RWTH University of Aachen, Aachen, Germany.
8
Division of Nephrology, RWTH University of Aachen, Aachen, Germany; Institute of Pathology, RWTH University of Aachen, Aachen, Germany; Institute of Molecular Biomedicine, Comenius University, Bratislava, Slovakia. Electronic address: pboor@ukaachen.de.

Abstract

Platelet-derived growth factor (PDGF)-D, a specific PDGF receptor β (PDGFR-β) ligand, mediates mesangial proliferation in vitro and in vivo. However, its role in renal development, physiology, and fibrosis is relatively unknown. In healthy murine kidneys, PDGF-D was found to be expressed on renal mesenchymal cells (mesangial cells, fibroblasts, and vascular smooth muscle cells). During renal fibrosis, PDGF-D and its receptor PDGFR-β were markedly and similarly upregulated in both human and murine kidneys on activated mesenchymal cells, but PDGF-D was also expressed de novo in injured renal tubular cells. The functional role of PDGF-D was studied in Pdgfd-/- mice, which showed no obvious spontaneous renal phenotype at a young age or during aging. Compared with wild-type littermates, Pdgfd-/- mice had significantly reduced renal interstitial fibrosis in two models of renal scarring: unilateral ureteral obstruction and unilateral ischemia/reperfusion injury. This was associated with reduced phosphorylation of PDGFR-β and its downstream mediator p38. Systemic adenoviral overexpression of PDGF-D in healthy mice resulted in increased collagen deposition in the kidney interstitium. Thus, PDGF-D is upregulated in murine and human kidney fibrosis, may mediate renal scarring, and is dispensable for normal kidney development and physiological functions. PDGF-D may be a suitable therapeutic target to combat kidney fibrosis.

KEYWORDS:

extracellular matrix; fibroblast; fibrosis; myofibroblast; platelet-derived growth factor

Comment in

PMID:
26924050
DOI:
10.1016/j.kint.2015.12.037
[Indexed for MEDLINE]

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