Abstract
BackgroundSERPINA1 is the gene for alpha-1 antitrypsin (AAT), an acute phase protein with anti-protease and immunoregulatory activities. Mutations in SERPINA1 gene cause AAT deficiency and predispose individuals to early-onset emphysema and liver diseases. Expression of the SERPINA1 gene is regulated by different promoters and alternative splicing events among non-coding exons 1A, 1B and 1C.MethodsWe have developed three quantitative PCR (QT-PCR) assays (1A, 1B and 1C). These assays were applied for the analysis of SERPINA1 alternative transcripts in: (1) 16 human tissues and (2) peripheral blood leukocytes from 33 subjects with AAT mutations and 7 controls.ResultsTissue-specific expression was found for the SERPINA1 transcripts. The 1A transcripts were mainly expressed in leukocytes and lung tissue while those detected with the 1B assay were highly restricted to leukocytes. Only 1B transcripts significantly correlated with serum AAT levels. The 1C transcripts were specifically found in lung, liver, kidney and pancreas. Furthermore, the expression of transcripts was related to AAT genotypes. While deficient variants of AAT had no pronounced effect on the transcript expression, null alleles were associated with significant reduction of different transcripts.ConclusionsThe possibility to discriminate between SERPINA1 alternative splicing products will help us to understand better the regulation of SERPINA1 gene and its association with SERPINA1 mutations-related diseases.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-015-0585-y) contains supplementary material, which is available to authorized users.
Highlights
SERPINA1 is the gene for alpha-1 antitrypsin (AAT), an acute phase protein with anti-protease and immunoregulatory activities
AAT is codified by the SERPINA1 gene, which is located on human chromosome 14q32 [2,3,4], mapped in the same cluster together with other serpin genes, SERPINA3 (α1-antichymotrypsin), SERPINA4, SERPINA5 (PCI, protein C inhibitor), SERPINA9, SERPINA10 (ZPI, protein Z-dependent protease inhibitor) as well as SERPINA11
Additional transcription initiation sites for SERPINA1 gene expression were proposed for corneal cells and A549 lung cell line [11,12,13]
Summary
SERPINA1 is the gene for alpha-1 antitrypsin (AAT), an acute phase protein with anti-protease and immunoregulatory activities. Expression of the SERPINA1 gene is regulated by different promoters and alter‐ native splicing events among non-coding exons 1A, 1B and 1C. Human alpha-1 antitrypsin (AAT), named alpha-1 proteinase inhibitor (α1-Pi) is the prototypic member of the serine protease inhibitor (SERPIN) superfamily of proteins [1]. The hepatocyte SERPINA1 promoter is located upstream of the hepatocyte transcription start site, within exon 1C [4, 6, 7]. An alternative promoter region, located upstream of exon 1A, controls SERPINA1 expression in other cells, Matamala et al J Transl Med (2015) 13:211 such as monocytes and macrophages [7]. Additional transcription initiation sites for SERPINA1 gene expression were proposed for corneal cells and A549 lung cell line [11,12,13]
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