CCN3 is a novel endogenous PDGF-regulated inhibitor of glomerular cell proliferation.
CCN3 is a novel endogenous PDGF-regulated inhibitor of glomerular cell proliferation.
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DOI：
10.1038/sj.ki.5002584
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发表时间：
2008
影响因子：
19.6
通讯作者：
C. V. Roeyen;Frank Eitner;T. Scholl;Peter Boor;U. Kunter;N. Planque;H. Gröne;A. Bleau;Bernard Perbal;Tammo Ostendorf;Juergen Floege
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文献类型：
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作者：
C. V. Roeyen;Frank Eitner;T. Scholl;Peter Boor;U. Kunter;N. Planque;H. Gröne;A. Bleau;Bernard Perbal;Tammo Ostendorf;Juergen Floege
CCN蛋白影响细胞增殖、迁移、附着和分化。我们在系膜细胞的cDNA阵列分析中发现，血小板衍生生长因子（PDGF）-BB或-DD刺激后，CCN 3被抑制，在体外生长停滞的系膜细胞过度表达和分泌CCN 3，而加入重组蛋白抑制细胞生长。通过PDGF-BB或特异性PDGF β受体配体PDGF-DD诱导系膜细胞增殖导致CCN 3 mRNA下调，证实了阵列研究。特异性PDGF α受体配体无影响。CCN 3蛋白在动脉平滑肌细胞、髓质平滑肌细胞和偶尔在健康大鼠肾脏的足细胞中被发现。肾小球CCN 3在系膜增殖前较低，但在系膜增殖性肾小球肾炎（GN）期间随着肾小球细胞增殖消退而增加。在系膜增生性疾病中抑制PDGF-B导致肾小球CCN 3 mRNA过表达。CCN 3主要定位于人肾小球的足细胞，但这种表达在不同的人肾小球肾炎中差异很大。在坏死性肾小球肾炎中，肾小球细胞增殖与CCN 3表达呈负相关。我们的研究确定CCN 3作为系膜细胞生长的内源性抑制剂和PDGF诱导的有丝分裂的调节剂。
CCN proteins affect cell proliferation, migration, attachment, and differentiation. We identified CCN3 as a suppressed gene following platelet-derived growth factor (PDGF)-BB or -DD stimulation in a cDNA-array analysis of mesangial cells.In vitrogrowth-arrested mesangial cells overexpressed and secreted CCN3, whereas the addition of the recombinant protein inhibited cell growth. Induction of mesangial cell proliferation by PDGF-BB or the specific PDGF β-receptor ligand PDGF-DD led to downregulation of CCN3 mRNA, confirming the array study. Specific PDGF α-receptor ligands had no effect. CCN3 protein was found in arterial smooth muscle cells, the medullary interstitium, and occasional podocytes in the healthy rat kidney. Glomerular CCN3 was low prior to mesangial proliferation but increased as glomerular cell proliferation subsided during mesangioproliferative glomerulonephritis (GN). Inhibition of PDGF-B in mesangioproliferative disease led to overexpression of glomerular CCN3 mRNA. CCN3 localized mostly to podocytes in human glomeruli, but this expression varied widely in different human glomerulonephritides. Glomerular cell proliferation negatively correlated with CCN3 expression in necrotizing GN. Our study identifies CCN3 as an endogenous inhibitor of mesangial cell growth and a modulator of PDGF-induced mitogenesis.