A new study has examined the role of the PLAUR gene, which encodes the urokinase-like plasminogen activator receptor (uPAR), and its splicing patterns, in DNA from patients with mild and severe hereditary angioedema (HAE) and from controls and found no difference between the two.
However, the results did show a different splicing pattern between monocyte-to-macrophage differentiation. The study was published in Molecular Biology Reports.
“Together with globular C1q receptor and cytokeratin 1, uPAR is involved in cellular mechanisms leading to bradykinin release,” the authors wrote. “Bradykinin represents the main mediator of HAE with clinical symptoms through increasing vascular permeability leading to edema in various body parts including subcutaneous tissue, gastrointestinal mucosa or oropharyngeal mucosa which can lead to a potentially life-threatening condition.”
Although previous studies have shown that uPAR isoforms are associated with certain diseases such as breast cancer, the exact function of the variants is unclear. However, during attacks of HAE, upregulation of uPAR was detected in peripheral blood mononuclear cells.
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The authors used reverse transcriptase-PCR electrophoresis to examine total RNA from 20 patients with mild HAE, 20 patients with severe HAE, and 20 healthy controls. cDNA was generated with a reverse transcription kit, and PLAUR splicing variants were detected to assess whether there were differences between the groups.
The results revealed no differences in splicing patterns of the PLAUR gene, suggesting no particular role for alternative splicing of this gene in terms of HAE manifestations or as a reflection of disease severity.
On the other hand, there were significant differences in the patterns between monocytes and macrophages in both the patients and the healthy controls. Specifically, they found a greater proportion of two isoforms, uPAR and suPAR, in macrophages compared with monocytes.
The significance of these differences in terms of disease status remains undetermined, and the authors recommend further studies designed to clarify this issue.
Ballonová L, Kulíšková P, Slanina P, et al. PLAUR splicing pattern in hereditary angioedema patients’ monocytes and macrophages. Mol Biol Rep. Published online April 22, 2023. doi.10.1007/s11033-023-08391-8