Abstract
It is critical to uncover genes specifically expressed in individual cell types for further understanding of cell biology and pathology. In order to elucidate pathogenesis of renal disease, we performed functional quantitative analysis of the genome in human kidney cells and compared the expression levels of a variety of kidney transcripts with those in other non-kidney cells. As a result, we identified a novel human gene, megsin, which is a new serine protease inhibitor (serpin) predominantly expressed in the kidney. Megsin is up-regulated in kidney disease. Genomic analysis revealed an association of the polymorphisms of megsin gene with susceptibility and/or progression of kidney disease. Its overexpression in rodents has led to the recognition of two different kidney abnormalities. The first disorder is linked to megsin biological effect itself and the other to its conformational abnormality recently called the serpinopathy. In the latter model, the cellular and tissue damage is induced by the endoplasmic reticulum (ER) stress due to conformational disorder resulting from megsin tertiary structure. In both types, the inhibition of megsin’s activity or abnormal conformational change should open new therapeutic perspectives. The desire to prevent these abnormalities with the hope to offer new therapeutic strategies has stimulated the development of megsin inhibitors by a structure based drug design approach relying on a precisely known three dimensional megsin structure.
Keywords: tissue specific gene, renal disease, serpin, serpinopathy, endoplasmic reticulum stress, structure based drug design (SBDD)
Current Genomics
Title: Megsin Gene: Its Genomic Analysis, Pathobiological Functions, and Therapeutic Perspectives
Volume: 8 Issue: 3
Author(s): Toshio Miyata, Ming Li, Xueqing Yu and Noriaki Hirayama
Affiliation:
Keywords: tissue specific gene, renal disease, serpin, serpinopathy, endoplasmic reticulum stress, structure based drug design (SBDD)
Abstract: It is critical to uncover genes specifically expressed in individual cell types for further understanding of cell biology and pathology. In order to elucidate pathogenesis of renal disease, we performed functional quantitative analysis of the genome in human kidney cells and compared the expression levels of a variety of kidney transcripts with those in other non-kidney cells. As a result, we identified a novel human gene, megsin, which is a new serine protease inhibitor (serpin) predominantly expressed in the kidney. Megsin is up-regulated in kidney disease. Genomic analysis revealed an association of the polymorphisms of megsin gene with susceptibility and/or progression of kidney disease. Its overexpression in rodents has led to the recognition of two different kidney abnormalities. The first disorder is linked to megsin biological effect itself and the other to its conformational abnormality recently called the serpinopathy. In the latter model, the cellular and tissue damage is induced by the endoplasmic reticulum (ER) stress due to conformational disorder resulting from megsin tertiary structure. In both types, the inhibition of megsin’s activity or abnormal conformational change should open new therapeutic perspectives. The desire to prevent these abnormalities with the hope to offer new therapeutic strategies has stimulated the development of megsin inhibitors by a structure based drug design approach relying on a precisely known three dimensional megsin structure.
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Cite this article as:
Miyata Toshio, Li Ming, Yu Xueqing and Hirayama Noriaki, Megsin Gene: Its Genomic Analysis, Pathobiological Functions, and Therapeutic Perspectives, Current Genomics 2007; 8 (3) . https://dx.doi.org/10.2174/138920207780833856
DOI https://dx.doi.org/10.2174/138920207780833856 |
Print ISSN 1389-2029 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5488 |
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