Suzuki D, Miyata T, Nangaku M, Takano H, Saotome N, Toyoda M, Mori Y, Zhang S Y, Inagi R, Endoh M, Kurokawa K, Sakai H
Division of Nephrology and Metabolism, Tokai University School of Medicine, Isehara, Kanagawa, Japan.
J Am Soc Nephrol. 1999 Dec;10(12):2606-13. doi: 10.1681/ASN.V10122606.
Mesangial cells play an important role in maintaining a structure and function of the glomerulus and in the pathogenesis of glomerular diseases. Recently, we discovered a new mesangium-predominant gene termed "megsin." Megsin is a novel protein that belongs to the serine protease inhibitor (serpin) superfamily. To elucidate the pathophysiologic role of megsin in the kidney, the expression and localization of megsin mRNA in renal tissues of patients with IgA nephropathy (IgA-N), diabetic nephropathy (DN), minimal change nephrotic syndrome (MCNS), membranous nephropathy (MN), and normal human kidney (NHK) was evaluated by in situ hybridization using digoxigenin-labeled oligonucleotide. Individual cells positive for megsin mRNA were observed only in glomeruli in all renal tissues. Their localization coincided with those of mesangial cells. The percentage of positive cells for megsin mRNA in total glomerular cells was significantly greater in IgA-N than in MCNS, MN, and NHK. It was also significantly greater in DN than in MCNS and NHK. In IgA-N, the percentage of megsin mRNA-positive cells was greater in tissues from those with mesangial cell proliferation and slightly mesangial matrix expansion (periodic acid-Schiff-positive area in the total glomerulus area, <30%; cell number in mesangial matrix area, >30; assessed in cross-sections through their vascular poles) than in tissues from those with severe mesangial matrix expansion (periodic acid-Schiff-positive area in total glomerulus area, >30%; cell number in mesangial matrix area, <30). In conclusion, megsin mRNA was predominantly expressed in glomerular mesangial cells in all renal tissues. The expression of megsin mRNA was upregulated in IgA-N and DN, both of which are diseases accompanied with mesangial cell proliferation and/or mesangial matrix expansion. These data suggest a link of megsin expression to the pathogenesis of IgA-N and DN, two major causes of end-stage renal failure.
系膜细胞在维持肾小球的结构和功能以及肾小球疾病的发病机制中发挥着重要作用。最近，我们发现了一种新的以系膜为主的基因，称为“megsin”。Megsin是一种新型蛋白质，属于丝氨酸蛋白酶抑制剂（serpin）超家族。为了阐明megsin在肾脏中的病理生理作用，我们采用地高辛标记的寡核苷酸原位杂交技术，评估了IgA肾病（IgA-N）、糖尿病肾病（DN）、微小病变肾病综合征（MCNS）、膜性肾病（MN）患者及正常人类肾脏（NHK）肾组织中megsin mRNA的表达和定位。在所有肾组织中，仅在肾小球中观察到megsin mRNA阳性的单个细胞。它们的定位与系膜细胞的定位一致。IgA-N中megsin mRNA阳性细胞在总肾小球细胞中的百分比显著高于MCNS、MN和NHK。DN中的该百分比也显著高于MCNS和NHK。在IgA-N中，系膜细胞增殖和轻度系膜基质扩张（总肾小球面积中高碘酸-希夫阳性面积，<30%；系膜基质区域细胞数，>30；通过血管极的横截面评估）患者的组织中，megsin mRNA阳性细胞的百分比高于重度系膜基质扩张（总肾小球面积中高碘酸-希夫阳性面积，>30%；系膜基质区域细胞数，<30）患者的组织。总之，megsin mRNA在所有肾组织的肾小球系膜细胞中主要表达。Megsin mRNA的表达在IgA-N和DN中上调，这两种疾病均伴有系膜细胞增殖和/或系膜基质扩张。这些数据表明megsin表达与IgA-N和DN的发病机制有关，这两种疾病是终末期肾衰竭的两个主要原因。
