Ophascharoensuk V, Fero M L, Hughes J, Roberts J M, Shankland S J
Department of Medicine, University of Washington School of Medicine, Seattle 98195-6521, USA.
Nat Med. 1998 May;4(5):575-80. doi: 10.1038/nm0598-575.
The cyclin-dependent kinase inhibitor p27Kip1 controls cell proliferation in response to normal mitogenic stimuli. We show here that p27Kip1 also safeguards against excessive cell proliferation in specific pathophysiologic settings. We used experimental glomerulonephritis as a paradigm for immune mediated inflammation and ureteral obstruction as a model for non-immune mediated inflammation. Renal function was substantially decreased in nephritic p27-/- mice compared with control mice, and this was associated with increased glomerular cell proliferation, apoptosis and matrix protein accumulation. Tubular epithelial cell proliferation and apoptosis was also increased in p27-/- mice following ureteral obstruction. p27Kip1 may have a general role in protecting cells and tissues from inflammatory injury.
细胞周期蛋白依赖性激酶抑制剂p27Kip1可响应正常的促有丝分裂刺激来控制细胞增殖。我们在此表明，p27Kip1在特定病理生理环境中也能防止细胞过度增殖。我们将实验性肾小球肾炎用作免疫介导炎症的范例，将输尿管梗阻用作非免疫介导炎症的模型。与对照小鼠相比，患肾炎的p27基因敲除小鼠的肾功能显著下降，这与肾小球细胞增殖、凋亡及基质蛋白积累增加有关。输尿管梗阻后，p27基因敲除小鼠的肾小管上皮细胞增殖和凋亡也增加。p27Kip1在保护细胞和组织免受炎性损伤方面可能具有普遍作用。
