Cheah Faang Y, Baltic Svetlana, Temple Suzanna E L, Bhoola Kanti, Thompson Philip J
Molecular Genetics and Inflammation Unit, Lung Institute of Western Australia (LIWA), Perth, Western Australia, Australia ; Centre for Asthma, Allergy and Respiratory Research (CAARR), School of Medicine and Pharmacology, University of Western Australia, Perth, Western Australia, Australia.
Molecular Genetics and Inflammation Unit, Lung Institute of Western Australia (LIWA), Perth, Western Australia, Australia ; Centre for Asthma, Allergy and Respiratory Research (CAARR), School of Medicine and Pharmacology, University of Western Australia, Perth, Western Australia, Australia ; Department of Cellular Pathology, Ausiral University of Chile, Valdivia, Chile.
PLoS One. 2014 Jan 27;9(1):e87175. doi: 10.1371/journal.pone.0087175. eCollection 2014.
The kinin B₁ receptor (B₁R) is rapidly upregulated after tissue trauma or inflammation and is involved in cancer and inflammatory diseases such as asthma. However, the role of the: promoter; a postulated alternative promoter; and spliced variants in airway epithelial and other lung cells are poorly understood. We identified, in various lung cell lines and leucocytes, a novel, naturally occurring splice variant (SV) of human B₁R gene with a shorter 5'untranslated region. This novel SV is ≈35% less stable than the wild-type (WT) transcript in lung adenocarcinoma cells (H2126), but does not influence translation efficiency. Cell-specific differences in splice variant expression were observed post des[Arg10]-kallidin stimulation with delayed upregulation of SV compared to WT suggesting potentially different regulatory responses to inflammation. Although an alternative promoter was not identified in our cell-lines, several cell-specific regulatory elements within the postulated alternative promoter region (negative response element (NRE) -1020 to -766 bp in H2126; positive response element (PRE) -766 to -410 bp in 16HBE; -410 to +1 region acts as a PRE in H2126 and NRE in 16HBE cells) were found. These findings reveal complex regulation of B₁R receptor expression in pulmonary cells which may allow future therapeutic manipulation in chronic pulmonary inflammation and cancer.
激肽B₁受体（B₁R）在组织创伤或炎症后迅速上调，并参与癌症和哮喘等炎症性疾病。然而，人们对其启动子、假定的替代启动子以及气道上皮细胞和其他肺细胞中的剪接变体的作用了解甚少。我们在各种肺细胞系和白细胞中鉴定出一种新的、天然存在的人B₁R基因剪接变体（SV），其5'非翻译区较短。在肺腺癌细胞（H2126）中，这种新的SV比野生型（WT）转录本的稳定性低约35%，但不影响翻译效率。在用去[精氨酸10] - 缓激肽刺激后，观察到剪接变体表达存在细胞特异性差异，与WT相比，SV的上调延迟，这表明对炎症可能有不同的调节反应。虽然在我们的细胞系中未鉴定出替代启动子，但在假定的替代启动子区域内发现了几个细胞特异性调节元件（H2126中负反应元件（NRE）-1020至-766 bp；16HBE中正向反应元件（PRE）-766至-410 bp；-410至+1区域在H2126中作为PRE，在16HBE细胞中作为NRE）。这些发现揭示了肺细胞中B₁R受体表达的复杂调节，这可能为未来慢性肺部炎症和癌症的治疗操作提供依据。
