A MESANGIUM-PREDOMINANT GENE, MEGSIN, IS A NEW SERPIN UNREGULATED IN IGA NEPHROPATHY

Mesangial cells play an important role in maintaining a structure and function of the glomerulus and in the pathogenesis of glomerular disea ses. To identify a specific gene expressed in human mesangial cells, w e used a rapid large-scale DNA sequencing and computerized data proces sing to compare the transcripts in cultured human mesangial cells with various different cells and organs. Using this novel approach, we dis covered a new mesangium-predominant gene termed ''megsin.'' We obtaine d a full-length cDNA clone of megsin, which coded for a novel 380-amin o acid protein. Amino acid homology search revealed that megsin belong ed to the serpin (serine protease inhibitor) superfamily, The amino ac id 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 wa s predominantly expressed in human mesangial cells. In situ hybridizat ion studies showed the megsin expression in the mesangium of normal gl omeruli, while it increased in the expanded mesangium of glomeruli fro m patients with IgA nephropathy with the degree of mesangial prolifera tion. Here we report a new human mesangium-predominant gene that may f unction as an inhibitory serpin in normal and abnormal biological proc esses of glomerulus.