RGD Reference Report - Cloning of rodent megsin revealed its up-regulation in mesangioproliferative nephritis. - Rat Genome Database

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Cloning of rodent megsin revealed its up-regulation in mesangioproliferative nephritis.

Authors: Nangaku, M  Miyata, T  Suzuki, D  Umezono, T  Hashimoto, T  Wada, T  Yagi, M  Nagano, N  Inagi, R  Kurokawa, K 
Citation: Nangaku M, etal., Kidney Int 2001 Aug;60(2):641-52.
RGD ID: 70611
Pubmed: PMID:11473647   (View Abstract at PubMed)
DOI: DOI:10.1046/j.1523-1755.2001.060002641.x   (Journal Full-text)

BACKGROUND: We recently cloned a new human mesangium-predominant gene, megsin. Megsin is a novel member of the serine protease inhibitor (serpin) superfamily. To elucidate functional roles of this gene, we cloned megsin in rodents and investigated its role in a rat nephritis model. METHODS: Megsin homologues were cloned from cultured rat and mouse mesangial cDNAs utilizing polymerase chain reaction (PCR) with degenerative primers. Expression of megsin in three different types of resident glomerular cells was investigated by PCR. Levels of megsin mRNA expression at various time points in the anti-Thy1 rat nephritis model were studied by semiquantitative PCR and Northern blotting analysis. In order to investigate megsin protein expression in anti-Thy1 nephritis rats, we raised antibody against rat megsin-specific synthetic peptide, with which immunohistochemical studies were performed. RESULTS: Rat and mouse megsins were composed of 380 amino acids, which revealed 75.3 and 73.9% identity, respectively, with human megsin at the amino acid level. Characteristic features as an inhibitory serpin were conserved in both rat and megsin megsins. PCR analysis revealed expression of megsin in cultured mesangial cells but not in glomerular epithelial or endothelial cells. In anti-Thy1 nephritis rats, semiquantitative PCR and Northern blotting showed that expression of megsin mRNA was up-regulated in glomeruli at day 8. Immunohistochemical studies demonstrated the prominent accumulation of megsin in glomeruli at the same time point. Megsin was mainly localized in mesangial area. The megsin expression level returned to the basal level at day 28. CONCLUSION: Sequences of megsin were well conserved among different species. Rat megsin was also predominantly expressed in mesangial cells. Expression of megsin was up-regulated at the peak of hypercellularity and matrix accumulation in the mesangioproliferative glomerulonephritis model, suggesting that megsin may participate in the process of glomerulosclerosis by modulating extracellular matrix deposition or cell survival.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
nephritis  ISOSerpinb7 (Rattus norvegicus)70611; 70611 RGD 
nephritis  IEP 70611 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Serpinb7  (serpin family B member 7)

Genes (Mus musculus)
Serpinb7  (serine (or cysteine) peptidase inhibitor, clade B, member 7)

Genes (Homo sapiens)
SERPINB7  (serpin family B member 7)

Objects referenced in this article
Gene Ap3m2 adaptor related protein complex 3 subunit mu 2 Rattus norvegicus

Additional Information