Lai K N, Leung J C, Yeung V T, Lewis L K, Nicholls M G
Department of Medicine, University of Hong Kong, Hong Kong.
Biochem Biophys Res Commun. 1998 Mar 17;244(2):567-72. doi: 10.1006/bbrc.1998.8167.
Adrenomedullin (ADM) is a novel 52 amino acid peptide with a potent vasodilator effect. Gene expression of ADM is found in human kidney but the exact cell source in the kidney is uncertain. Its plasma level is raised in association with changes in sympathetic nervous activity and body fluid volume in hypertension and chronic renal failure. Herein, we examined the presence of mRNA encoding for ADM in cultured human glomerular cells. Adrenomedullin in cell culture supernatant was measured by a radio-immunoassay (with a detection level of 3.2 pmol/l). Adrenomedullin mRNA was found in cultured mesangial and glomerular epithelial cells as well as in vascular endothelial cells. Supernatant levels of ADM for cultured mesangial and glomerular epithelial cells were 21.2 and < 3.2 pmol/l respectively. Contrary to vascular smooth muscle cells, the gene expression for ADM in mesangial cells was up-regulated when incubated with increasing concentration of TNF-alpha or fetal bovine serum (FBS) but this effect was not observed with very high concentration. Parallel results were observed in adrenomedullin levels in supernatant from mesangial cell cultures. Forskolin, captopril, or TGF-beta had no effect on the transcription or synthesis of ADM in mesangial cells. The gene expression for ADM in glomerular epithelial cells was down-regulated when incubated with increasing concentration of TNF-alpha, forskolin or FBS. The ADM levels in all supernatant from resting glomerular epithelial cell cultures were < 3.2 pmol/l. Recent murine data show that ADM stimulates the release of cAMP but suppresses mitogenesis in cultured mesangial cells. Our results suggest ADM is synthesized by mesangial cells in an autocrine fashion and the peptide may potentially be involved in intra-renal blood pressure control.
肾上腺髓质素（ADM）是一种由52个氨基酸组成的新型肽，具有强大的血管舒张作用。在人类肾脏中可发现ADM的基因表达，但肾脏中确切的细胞来源尚不确定。在高血压和慢性肾衰竭患者中，其血浆水平会随着交感神经活动和体液量的变化而升高。在此，我们检测了培养的人肾小球细胞中编码ADM的mRNA的存在情况。通过放射免疫分析法（检测水平为3.2 pmol/l）测定细胞培养上清液中的肾上腺髓质素。在培养的系膜细胞、肾小球上皮细胞以及血管内皮细胞中均发现了肾上腺髓质素mRNA。培养的系膜细胞和肾小球上皮细胞的ADM上清液水平分别为21.2和<3.2 pmol/l。与血管平滑肌细胞不同，当系膜细胞与浓度不断增加的肿瘤坏死因子-α（TNF-α）或胎牛血清（FBS）孵育时，ADM的基因表达上调，但在极高浓度时未观察到这种效应。在系膜细胞培养上清液中的肾上腺髓质素水平也观察到了类似结果。福斯可林、卡托普利或转化生长因子-β（TGF-β）对系膜细胞中ADM的转录或合成没有影响。当与浓度不断增加的TNF-α、福斯可林或FBS孵育时，肾小球上皮细胞中ADM的基因表达下调。静止的肾小球上皮细胞培养物的所有上清液中的ADM水平均<3.2 pmol/l。最近的小鼠数据表明，ADM可刺激环磷酸腺苷（cAMP）的释放，但抑制培养的系膜细胞的有丝分裂。我们的结果表明，ADM由系膜细胞以自分泌方式合成，该肽可能参与肾内血压的控制。
