Floege Jürgen, van Roeyen Claudia, Boor Peter, Ostendorf Tammo
Division of Nephrology and Immunology, RWTH University of Aachen, Aachen, Germany.
Contrib Nephrol. 2007;157:153-8. doi: 10.1159/000102460.
In view of increasing numbers of patients with end-stage renal disease (ESRD), new approaches to common underlying diseases, such as mesangioproliferative glomerulonephritis, including IgA nephropathy, are urgently needed. Whereas the role of the platelet-derived growth factor (PDGF) B chain in mediating mesangioproliferative changes is well established, the role of the PDGF-D chain has only recently been elucidated. The PDGF-D chain, like PDGF-B, signals through the PDGF beta-receptor and therefore shares a number of biological activities with PDGF-B. Recent studies have shown that PDGF-D induces mesangial cell proliferation in vitro and is overexpressed in mesangioproliferative glomerulonephritis in vivo. Hepatic transfection with an adenoviral vector expressing PDGF-D induced prominent mesangioproliferative nephritis in mice, whereas antagonism of PDGF-D in a rat model of mesangioproliferative disease ameliorated the renal changes. These four observations establish PDGF-D, like -B, as an important mediator of mesangioproliferative nephritis in vivo and suggest that it may be an attractive therapeutic target. In addition, first observations suggest that PDGF-D may also contribute to secondary renal changes that characterize progressive renal failure, i.e. tubulointerstitial fibrosis.
鉴于终末期肾病（ESRD）患者数量不断增加，迫切需要针对常见基础疾病的新方法，如包括IgA肾病在内的系膜增生性肾小球肾炎。虽然血小板衍生生长因子（PDGF）B链在介导系膜增生性改变中的作用已得到充分证实，但PDGF-D链的作用直到最近才得以阐明。PDGF-D链与PDGF-B一样，通过PDGFβ受体发出信号，因此与PDGF-B具有许多生物学活性。最近的研究表明，PDGF-D在体外可诱导系膜细胞增殖，在体内系膜增生性肾小球肾炎中过表达。用表达PDGF-D的腺病毒载体进行肝脏转染可在小鼠中诱导显著的系膜增生性肾炎，而在系膜增生性疾病大鼠模型中拮抗PDGF-D可改善肾脏病变。这四项观察结果表明，与PDGF-B一样，PDGF-D是体内系膜增生性肾炎的重要介质，并表明它可能是一个有吸引力的治疗靶点。此外，初步观察结果表明，PDGF-D也可能导致进行性肾衰竭特征性的继发性肾脏改变，即肾小管间质纤维化。
