| First Author | Buhl EM | Year | 2016 |
| Journal | Kidney Int | Volume | 89 |
| Issue | 4 | Pages | 848-61 |
| PubMed ID | 26924050 | Mgi Jnum | J:325432 |
| Mgi Id | MGI:6781195 | Doi | 10.1016/j.kint.2015.12.037 |
| Citation | Buhl EM, et al. (2016) The role of PDGF-D in healthy and fibrotic kidneys. Kidney Int 89(4):848-61 |
| abstractText | Platelet-derived growth factor (PDGF)-D, a specific PDGF receptor beta (PDGFR-beta) 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-beta 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-beta 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. |
