GPR126 is an adhesion G protein‐coupled receptor which lies on chromosome 6q24. Genetic variants in this region are reproducibly associated with lung function and COPD in genome wide association studies (GWAS). The aims of this study were to define the role of GPR126 in the human lung and in pulmonary disease and identify possible casual variants. Online tools (GTEx and LDlink) identified SNPs which may have effects on GPR126 function/ expression, including missense variant Ser123Gly and an intronic variant that shows eQTL effects on GPR126 expression. GPR126 signaling via cAMP‐mediated pathways was identified in human structural airway cells when activated with the tethered agonist, stachel. RNA‐seq was used to identify downstream genes/ pathways affected by stachel‐mediated GPR126 activation in human airway smooth muscle cells. We identified ~350 differentially expressed genes at 4 and 24 hours post stimulation with ~20% overlap. We identified that genes regulated by GPR126 activation include IL33, CTGF, and SERPINE1, which already have known roles in lung biology. Pathways altered by GPR126 included those involved in cell cycle progression and cell proliferation. Here, we suggest a role for GPR126 in airway remodeling.

Eukaryotic initiation factor 3 (eIF3), encapsulated in liposomes, is taken up by chick muscle cells in culture. The exogenously supplied factor (isolated from 14-d embryonic muscle) rapidly associates with 40S ribosomal subunits and particles sedimenting at 80-1205 (the known sedimentation value of myosin heavy chain [MHC] mRNPs) . In addition, exogenously supplied eIF3 has a specific stimulatory effect on myofibrillar protein synthesis. This stimulation is most apparent at the onset of cell fusion and after the accumulation of MHC-mRNPs. As previously reported (8), total eIF3 can be fractionated on an MHC-mRNA affinity column into a "core" eIF3 and a high affinity component (HAF) which dictates the discriminatory activity of core eIF3 . Liposome-encapsulated core eIF3 delivered to cells is found predominantly in 40S ribosomal subunits and gives only a slight stimulation of total protein synthesis. When 3 H-MHC-mRNA, preincubated with HAF, is introduced into myoblasts via liposomes, the mRNA is found in heavy polysomes. On the other hand, when the messenger alone or with core eIF3 is taken up by the cells, it is found only on small polysomes. Similar experiments, using viral RNA with the HAF, show no increase in the size class of polysomes. These results mimic the differences observed between myoblast and myotube utilization of MHC-mRNA previously observed (17) . These results demonstrate the mRNA discriminatory activity of specific proteins associated with muscle eIF3 and suggest that these proteins play a role in mRNA activation and translation during muscle differentiation .

Genetic studies have identified several epithelial-derived genes associated with airway diseases. However, techniques used to study gene function frequently exceed the proliferative potential of primary human bronchial epithelial cells (HBECs) isolated from patients. Increased expression of the polycomb group protein BMI-1 extends the lifespan of HBECs while maintaining cell context plasticity. Herein we aimed to assess how BMI-1 expression impacted cellular functions and global mRNA expression. HBECs from six donors were transduced with lentivirus containing BMI-1 and cells were characterised, including by RNA sequencing and impedance measurement. BMI-1-expressing HBECs (B-HBECs) have a proliferative advantage and show comparable in vitro properties to low passage primary HBECs, including cell attachment/spreading and barrier formation. The B-HBEC mRNA signature was modestly different to HBECs, with only 293 genes differentially expressed (5% false discovery rate). Genes linked to epithelial mesenchymal transition and cell cycle were enriched in B-HBECs. We investigated the expression of genes implicated in asthma from genetic and expression studies and found that 97.6% of genes remained unaltered. We have shown that increased BMI-1 expression in HBECs delays lung epithelial cell senescence by promoting cell cycle progression and highlighted the flexible utility for B-HBECs as an important platform for studying airway epithelial mechanisms.