Matsumoto Michitaka, Fujimoto Shouichi, Iwatsubo Shuji, Sato Yuji, Hara Seiichiro, Kitamura Kazuo, Eto Tanenao
First Department of Internal Medicine, Miyazaki Medical College, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki-gun, Miyazaki, 889-1692 Japan.
Clin Exp Nephrol. 2004 Dec;8(4):316-21. doi: 10.1007/s10157-004-0309-8.
Adrenomedullin (AM) has antiproliferative and proapoptotic effects on mesangial cells in culture, but the regulation of AM and its receptors in glomeruli with glomerulonephritis have not been clarified.
We examined sequential changes in the mRNA expression of AM and its receptors (receptor-activity-modifying proteins; RAMPs), and AM production in the glomeruli of Thy.1 glomerulonephritis, using quantitative reverse transcription-polymerase chain reaction (RT-PCR) and immunoradiometric assay (IRMA).
Both the mRNA and the protein levels of AM in glomeruli isolated from rats 7 days after injection with anti-thymocyte serum (ATS), when mesangial cell proliferation peaked, were unchanged compared with those in control rats. However, on day 14, when almost all glomeruli had appeared to return to normal, AM mRNA expression was significantly increased (day 14 vs control: 51.2 +/- 9.1 vs 28.4 +/- 7.1 (mmol/mol glyceraldehyde-3-phosphate dehydrogenase; GAPDH); P < 0.05), as was the AM concentration (12.0 +/- 0.8 vs 8.4 +/- 0.4 fmol/10(4) glomeruli; P < 0.01). Subsequently, by 28 days after ATS injection, both levels decreased to the control ones. The mRNA expression of AM and RAMP2, in the glomeruli of Thy.1 glomerulonephritis changed similarly over time. Immunohistochemical staining revealed that AM production in mesangial cells was increased predominantly on day 14.
AM and RAMP increased during the reso-lution phase of increased mesangial proliferation in Thy.1 glomerulonephritis, but not during the mesangial proliferative phase. Considering the antiproliferative and proapoptotic effects of AM, its action on mesangial cells may be related to the amelioration of glomerulonephritis.
肾上腺髓质素（AM）对培养的系膜细胞具有抗增殖和促凋亡作用，但肾小球肾炎时肾小球中AM及其受体的调节尚未阐明。
我们使用定量逆转录-聚合酶链反应（RT-PCR）和免疫放射分析（IRMA），检测了Thy.1肾小球肾炎大鼠肾小球中AM及其受体（受体活性修饰蛋白；RAMPs）的mRNA表达以及AM的产生随时间的变化。
注射抗胸腺细胞血清（ATS）7天后，当系膜细胞增殖达到峰值时，分离的大鼠肾小球中AM的mRNA和蛋白水平与对照大鼠相比没有变化。然而，在第14天，当几乎所有肾小球似乎已恢复正常时，AM mRNA表达显著增加（第14天与对照相比：51.2±9.1对28.4±7.1（毫摩尔/摩尔甘油醛-3-磷酸脱氢酶；GAPDH）；P<0.05），AM浓度也增加（12.0±0.8对8.4±0.4飞摩尔/10⁴个肾小球；P<0.01）。随后，到ATS注射后28天，两者水平均降至对照水平。Thy.1肾小球肾炎肾小球中AM和RAMP2的mRNA表达随时间变化相似。免疫组织化学染色显示，系膜细胞中AM的产生主要在第14天增加。
在Thy.1肾小球肾炎系膜增殖增加的消退期，AM和RAMP增加，但在系膜增殖期不增加。考虑到AM的抗增殖和促凋亡作用，其对系膜细胞的作用可能与肾小球肾炎的改善有关。
