title: Expression of megsin mRNA, a novel mesangium-predominant gene, in the renal tissues of various glomerular diseases.
abstract: 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.
authors.affiliation: Division of Nephrology and Metabolism, Tokai University School of Medicine, Isehara, Kanagawa, Japan.
authors.forename: D
authors.initials: D
authors.lastname: Suzuki
authors.forename: T
authors.initials: T
authors.lastname: Miyata
authors.forename: M
authors.initials: M
authors.lastname: Nangaku
authors.forename: H
authors.initials: H
authors.lastname: Takano
authors.forename: N
authors.initials: N
authors.lastname: Saotome
authors.forename: M
authors.initials: M
authors.lastname: Toyoda
authors.forename: Y
authors.initials: Y
authors.lastname: Mori
authors.forename: S Y
authors.initials: SY
authors.lastname: Zhang
authors.forename: R
authors.initials: R
authors.lastname: Inagi
authors.forename: M
authors.initials: M
authors.lastname: Endoh
authors.forename: K
authors.initials: K
authors.lastname: Kurokawa
authors.forename: H
authors.initials: H
authors.lastname: Sakai
mesh_terms: D000199:Actins / Q000378:metabolism; D000328:Adult; D001483:Base Sequence; D018076:DNA, Complementary / Q000235:genetics; D003928:Diabetic Nephropathies / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D005260:Female; D015870:Gene Expression; D005920:Glomerular Mesangium / Q000378:metabolism / Q000473:pathology; D005922:Glomerulonephritis, IGA / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015433:Glomerulonephritis, Membranous / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D006801:Humans; D017403:In Situ Hybridization; D007668:Kidney / Q000378:metabolism*; D007674:Kidney Diseases / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009402:Nephrosis, Lipoid / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism*; D015843:Serpins / Q000235:genetics*
chemical_list: D000199:Actins; D018076:DNA, Complementary; D018809:Proliferating Cell Nuclear Antigen; D012333:RNA, Messenger; C114170:SERPINB7 protein, human; D015843:Serpins