A mesangium-predominant gene, megsin, is a new serpin upregulated in IgA nephropathy

Toshio Miyata, Masaomi Nangaku, Daisuke Suzuki, Reiko Inagi, Ken Ichi Uragami, Hideto Sakai, Kousaku Okubo, Kiyoshi Kurokawa

Research output: Contribution to journalArticlepeer-review

75 Citations (Scopus)

Abstract

Mesangial cells play an important role in maintaining a structure and function of the glomerulus and in the pathogenesis of glomerular diseases. To identify a specific gene expressed in human mesangial cells, we used a rapid largescale DNA sequencing and computerized data processing to compare the transcripts in cultured human mesangial cells with various different cells and organs. Using this novel approach, we discovered a new mesangium- predominant gene termed 'megsin.' We obtained a full-length cDNA clone of megsin, which coded for a novel 380-amino acid protein. Amino acid homology search revealed that megsin belonged to the serpin (serine protease inhibitor) superfamily. The amino acid sequences in the reactive loop site of megsin showed characteristic features of functional serpins. Northern blot and reverse-transcribed PCR analyses of various tissues and cells demonstrated that megsin was predominantly expressed in human mesangial cells. 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. Here we report a new human mesangium-predominant gene that may function as an inhibitory serpin in normal and abnormal biological processes of glomerulus.

Original languageEnglish
Pages (from-to)828-836
Number of pages9
JournalJournal of Clinical Investigation
Volume102
Issue number4
DOIs
Publication statusPublished - 1998 Aug 15
Externally publishedYes

Keywords

  • 3'-directed cDNA library
  • Cell-specific protein
  • Glomerulonephritis
  • Mesangial proliferation
  • Serpin

ASJC Scopus subject areas

  • Medicine(all)

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