Disease relevance of SERPINB7

• The amount of megsin protein was increased in glomeruli of patients with IgA nephropathy than in those of normal individuals and of patients with minimal change nephrotic syndrome or membranous nephropathy, suggesting a pathophysiological role of megsin as a functional modulator of mesangial functions in situ [1].
• These data suggest a link of megsin expression to the pathogenesis of IgA-N and DN, two major causes of end-stage renal failure [2].
• CONCLUSION: In this Chinese population, the 2093C-2180T haplotype at the 3'UTR of MEGSIN gene is associated with more severe forms of IgAN, and more rapid disease progression [3].

High impact information on SERPINB7

• Northern blot and reverse-transcribed PCR analyses of various tissues and cells demonstrated that megsin was predominantly expressed in human mesangial cells [4].
• A mesangium-predominant gene, megsin, is a new serpin upregulated in IgA nephropathy [4].
• Amino acid homology search revealed that megsin belonged to the serpin (serine protease inhibitor) superfamily [4].
• The amino acid sequences in the reactive loop site of megsin showed characteristic features of functional serpins [4].
• Novel serpinopathy in rat kidney and pancreas induced by overexpression of megsin [5].

Biological context of SERPINB7

• Genetic variation in Megsin confers susceptibility to IgAN [6].
• This study investigates the regulatory mechanisms of megsin gene expression [7].
• The analysis for exon-intron junctions of megsin genomic DNA demonstrated that the gene contained 8 exons and 7 introns, spanned 20 kbp, and that the genomic structure of the serpin superfamily was highly conserved [7].
• Fluorescence in situ hybridization (FISH) revealed that the megsin gene is localized in chromosome 18q21.3, close to the other serpin genes [7].
• A genomic clone of the human megsin gene was obtained by screening bacterial artificial chromosome (BAC) library with the megsin cDNA [7].

Anatomical context of SERPINB7

• Megsin (SERPINB7) is an important candidate gene, predominantly expressed in glomerular mesangium and upregulated in IgAN [6].
• The sequence and reporter analyses on 4021-bp-long 5'-flanking region of megsin gene demonstrated a consensus promoter segment within this region and a relatively strong promoter activity in human mesangial cells and A431, a human tumor cell line recently reported to express a novel serpin identical with megsin [7].
• Extracts of isolated glomeruli from megsin transgenic rats reveal marked up-regulation of ER stress chaperones in podocytes, which was supported by immunohistochemical analysis [8].
• Transgenic rats overexpressing megsin (Tg meg), a newly identified serine protease inhibitor (serpin), demonstrated intraneuronal periodic-acid Schiff (PAS)-positive inclusions distributed throughout deeper layers of cerebral cortex, CA1 of the hippocampus, and substantia nigra [9].

Other interactions of SERPINB7

• Recently, we discovered a new mesangium-predominant gene termed "megsin." Megsin is a novel protein that belongs to the serine protease inhibitor (serpin) superfamily [2].
• Interestingly, STM91-01 expressed megsin, a novel marker for mesangial cells, in addition to angiopoietin-1 [10].

Analytical, diagnostic and therapeutic context of SERPINB7

• In situ hybridization studies showed the megsin expression in the mesangium of normal glomeruli, while it increased in the expanded mesangium of glomeruli from patients with IgA nephropathy with the degree of mesangial proliferation [4].
• They correspond to electron-dense deposits, shown to contain megsin by immunohistochemistry and immunoelectron microscopy [5].
• By immunohistochemistry, megsin protein was specifically identified in the mesangial area [1].
• Here we investigate expression of ER stress proteins in cultured rat podocytes as well as in our recently developed animal model of abnormal protein retention within the ER of podocytes (i.e., megsin transgenic rat) [8].

References