Canaan-Kühl S, Ostendorf T, Zander K, Koch K M, Floege J
Division of Nephrology, Medizinische Hochschule, Hannover, Germany.
Kidney Int. 1998 May;53(5):1143-51. doi: 10.1046/j.1523-1755.1998.00895.x.
Local C-type natriuretic peptide (CNP) production and CNP receptor expression have been demonstrated in glomeruli. However, the glomerular (patho-)physiological functions of CNP are largely unknown. We therefore investigated the effects of CNP on mesangial cell proliferation and matrix accumulation in the rat mesangioproliferative anti-Thy 1.1 model. Over seven days rats received a continuous infusion (1 microgram/kg/min) of either CNP (N = 6), an irrelevant control peptide (N = 3) or buffer alone (N = 6). Kidney biopsies were performed on days 2, 4 and 8. Few significant differences between the groups were noted on days 2 and 4. Compared to buffer treated rats on day 8, those receiving CNP showed a 35% reduction of glomerular mitoses, a 62% reduction of glomerular uptake of the thymidine analogue BrdU and a significant reduction in glomerular expression of PDGF B-chain. Double immunoperoxidase staining also revealed blunting of proliferating, activated mesangial cells (515 reduction of alpha-smooth muscle actin-/BrdU-positive cells) and macrophage influx. Moreover, there was a marked reduction of mesangial collagen IV and fibronectin accumulation at the protein and mRNA level. Rats receiving the control peptide were indistinguishable from buffer treated rats. Systemic blood pressure was reduced by 10 to 20% in both CNP and control peptide treated rats on day 8, excluding that the findings were due to hemodynamic effects of CNP. Our findings demonstrate that CNP is involved in the regulation of mesangial cell proliferation and matrix production in vivo. The data suggest the existence of a glomerular natriuretic peptide system that may regulate tissue homeostasis and contribute to resolution of mesangioproliferative diseases.
肾小球中已证实存在局部C型利钠肽（CNP）的产生及CNP受体表达。然而，CNP在肾小球的（病理）生理功能在很大程度上尚不清楚。因此，我们在大鼠系膜增生性抗Thy 1.1模型中研究了CNP对系膜细胞增殖和基质积聚的影响。在七天时间里，大鼠持续输注（1微克/千克/分钟）CNP（N = 6）、无关对照肽（N = 3）或仅输注缓冲液（N = 6）。在第2、4和8天进行肾活检。在第2天和第4天，各组之间几乎没有显著差异。与第8天接受缓冲液处理的大鼠相比，接受CNP的大鼠肾小球有丝分裂减少35%，胸腺嘧啶类似物BrdU的肾小球摄取减少62%，血小板衍生生长因子B链的肾小球表达显著降低。双重免疫过氧化物酶染色还显示增殖、活化的系膜细胞减少（α-平滑肌肌动蛋白/BrdU阳性细胞减少515）以及巨噬细胞浸润减少。此外，在蛋白质和mRNA水平上，系膜IV型胶原和纤连蛋白的积聚明显减少。接受对照肽的大鼠与接受缓冲液处理的大鼠没有区别。在第8天，接受CNP和对照肽处理的大鼠的全身血压均降低了10%至20%，排除了这些发现是由于CNP的血流动力学效应所致。我们的研究结果表明，CNP参与体内系膜细胞增殖和基质产生的调节。数据表明存在一种肾小球利钠肽系统，其可能调节组织稳态并有助于系膜增生性疾病的消退。
