ILC2 is a surrogate marker of airway eosinophilic inflammation in patients with mild to moderate asthma and has great potential advantages for selecting the asthmatic patients most likely to benefit from therapeutics targeting Th2 inflammation.

BackgroundAirway remodeling is a repair process that occurs after injury resulting in increased airway hyper-responsiveness in asthma. Thymic stromal lymphopoietin (TSLP), a vital cytokine, plays a critical role in orchestrating, perpetuating and amplifying the inflammatory response in asthma. TSLP is also a critical factor in airway remodeling in asthma.ObjectivesTo examine the role of TSLP-induced cellular senescence in airway remodeling of asthma in vitro and in vivo.MethodsCellular senescence and airway remodeling were examined in lung specimens from patients with asthma using immunohischemical analysis. Both small molecule and shRNA approaches that target the senescent signaling pathways were used to explore the role of cellular senescence in TSLP-induced airway remodeling in vitro. Senescence-Associated β-galactosidase (SA-β-Gal) staining, and BrdU assays were used to detect cellular senescence. In addition, the Stat3-targeted inhibitor, WP1066, was evaluated in an asthma mouse model to determine if inhibiting cellular senescence influences airway remodeling in asthma.ResultsActivation of cellular senescence as evidenced by checkpoint activation and cell cycle arrest was detected in airway epithelia samples from patients with asthma. Furthermore, TSLP-induced cellular senescence was required for airway remodeling in vitro. In addition, a mouse asthma model indicates that inhibiting cellular senescence blocks airway remodeling and relieves airway resistance.ConclusionTSLP stimulation can induce cellular senescence during airway remodeling in asthma. Inhibiting the signaling pathways of cellular senescence overcomes TSLP-induced airway remodeling.

Growing evidence has highlighted the roles of circular RNAs (circRNAs) in non-small-cell lung cancer (NSCLC), however, their roles in NSCLC glycolysis remains poorly understood. CircRNAs microarray profiles discovered a novel exon-derived circRNA, circSLC25A16 (hsa_circ_0018534), in NSCLC tissue samples. In NSCLC samples, high-expression of circSLC25A16 was associated with unfavorable prognosis. Cellular experiments revealed that circSLC25A16 accelerated the glycolysis and proliferation of NSCLC cells. Besides, circSLC25A16 knockdown repressed the in vivo growth by xenograft assays. RNA-fluorescence in situ hybridization (RNA-FISH) illustrated that circSLC25A16 and miR-488-3p were both located in cytoplasm. Mechanistic experiments demonstrated that circSLC25A16 interacts with miR-488-3p/HIF-1α, which activates lactate dehydrogenase A (LDHA) by facilitating its transcription. Collectively, present research reveals the crucial function of circSLC25A16 on NSCLC glycolysis through miR-488-3p/HIF-1α/LDHA, suggesting the underlying pathogenesis for NSCLC and providing a therapeutic strategy for precise treatment.

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This study aimed to identify the role and regulation of thymic stromal lymphopoietin (TSLP) in asthmatic airway remodelling. To identify the expression of TSLP, α smooth muscle actin (α-SMA) and collagen I in bronchial tissues, bronchial biopsy specimens were collected from patients with asthma and healthy controls and stained with specific antibodies, respectively. To characterize the signalling pathways regulated by TSLP, we silenced or overexpressed TSLP in human lung fibroblast (HLF-1) cells by shRNA approaches or transfection and detected the expression of TSLP receptor (TSLPR) by enzyme-linked immunosorbent assay and Western blot analysis. In TSLP signalling pathway, the protein expression of total signal transducer and activator of transcription 3 (STAT3), STAT5, the phosphorylation of STAT3 (pSTAT3) and STAT5 (pSTAT5), TSLP, α-SMA and collagen I were also detected by Western blotting. In addition, the α-SMA, collagen I and mRNA expression were determined by real-time reverse-transcription. To further confirm the TSLP-STAT3 signalling pathway in HLF-1 cells, we inhibited STAT3 activity by targeted small molecules and then detected TSLP-induced expression of α-SMA and collagen I in both mRNA and protein levels by quantitative real-time reverse-transcription and Western blotting, respectively. First, overexpression of TSLP, α-SMA and collagen I was detected in epithelium collected from patients with asthma. Second, STAT3 activity and the expression of α-SMA and collagen I were controlled, regulated by TSLP. Specifically, the pSTAT3, α-SMA and collagen I were induced by the introduction of TSLP in HLF-1 cells, and the repression of α-SMA and collagen I was detected after TSLP silencing. Third, no changes of pSTAT5 were found in the presence of the STAT3 inhibitor, and TSLP-induced α-SMA and collagen I upregulation is in a STAT3 dependent manner. If we inhibit STAT3 activity by STAT3 targeted small molecules, TSLP-induced α-SMA and collagen I upregulation cannot be detected. The functions of TSLP in asthmatic airway remodelling were performed through STAT3 signalling pathway.