Allergy, asthma & immunology research · 2026
E2F1-Activated lncRNA FTX Promotes Asthma Progression via Regulating the SRSF1/RBPJ Axis.
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Lai Yuting, Qiu Guoqing, Li Na, Chen Yuming, Shen Yan
Аннотация
PURPOSE: Long non-coding RNA five prime to Xist (FTX) is considered a regulator for asthma. Therefore, we aimed to explore its more roles and molecular mechanisms in asthma process.
METHODS: Serum samples from controls and asthmatics were collected. Asthma mouse models were induced with ovalbumin (OVA), and cell models were established using airway smooth muscle cells (ASMCs) treated with platelet-derived growth factor BB (PDGF-BB). The inspiratory and expiratory airway resistances of mice were examined by measuring airway hyperresponsiveness. The pathological changes of mice lung tissues were observed by hematoxylin & eosin, periodic acid-Schiff, and Masson staining. Serum immunoglobulin E and inflammatory factor levels were detected using an enzyme-linked immunosorbent assay. The CCK-8, Transwell, and flow cytometry were used to assess cell function. FTX, E2F family transcription factor 1 (E2F1), serine rich/arginine splicing factor 1 (SRSF1), and recombination signal binding protein J (RBPJ) levels measured by quantitative real-time-polymerase chain reaction or Western blotting. The relationships among FTX, E2F1, SRSF1, and RBPJ were evaluated by dual-luciferase report, ChIP, RNA pull-down and RIP assay. The effect of FTX/SRSF1 on RBPJ mRNA stability was analyzed by the actinomycin D treatment assay.
RESULTS: Upregulated FTX was detected in asthmatic patients, asthma mice, and PDGF-BB-induced ASMCs. FTX downregulation repressed PDGF-BB-induced ASMCs viability, migration, and inflammation. E2F1 bound to the FTX promoter region to activate its expression, and E2F1 downregulation could repress PDGF-BB-induced ASMCs function via reducing FTX expression. Also, FTX stabilized RBPJ mRNA by interacting with SRSF1. RBPJ overexpression reversed the downregulation effect of FTX knockdown on PDGF-BB-induced ASMCs viability, migration, and inflammation. Meanwhile, E2F1 downregulation alleviated mouse asthma symptoms by inhibiting the FTX/SRSF1/RBPJ pathway.
CONCLUSIONS: FTX, transcriptionally activated by E2F1, promoted asthma progression via the the regulation of the SRSF1/RBPJ pathway, thereby providing a possible therapeutic target for asthma treatment that warrants further validation.
METHODS: Serum samples from controls and asthmatics were collected. Asthma mouse models were induced with ovalbumin (OVA), and cell models were established using airway smooth muscle cells (ASMCs) treated with platelet-derived growth factor BB (PDGF-BB). The inspiratory and expiratory airway resistances of mice were examined by measuring airway hyperresponsiveness. The pathological changes of mice lung tissues were observed by hematoxylin & eosin, periodic acid-Schiff, and Masson staining. Serum immunoglobulin E and inflammatory factor levels were detected using an enzyme-linked immunosorbent assay. The CCK-8, Transwell, and flow cytometry were used to assess cell function. FTX, E2F family transcription factor 1 (E2F1), serine rich/arginine splicing factor 1 (SRSF1), and recombination signal binding protein J (RBPJ) levels measured by quantitative real-time-polymerase chain reaction or Western blotting. The relationships among FTX, E2F1, SRSF1, and RBPJ were evaluated by dual-luciferase report, ChIP, RNA pull-down and RIP assay. The effect of FTX/SRSF1 on RBPJ mRNA stability was analyzed by the actinomycin D treatment assay.
RESULTS: Upregulated FTX was detected in asthmatic patients, asthma mice, and PDGF-BB-induced ASMCs. FTX downregulation repressed PDGF-BB-induced ASMCs viability, migration, and inflammation. E2F1 bound to the FTX promoter region to activate its expression, and E2F1 downregulation could repress PDGF-BB-induced ASMCs function via reducing FTX expression. Also, FTX stabilized RBPJ mRNA by interacting with SRSF1. RBPJ overexpression reversed the downregulation effect of FTX knockdown on PDGF-BB-induced ASMCs viability, migration, and inflammation. Meanwhile, E2F1 downregulation alleviated mouse asthma symptoms by inhibiting the FTX/SRSF1/RBPJ pathway.
CONCLUSIONS: FTX, transcriptionally activated by E2F1, promoted asthma progression via the the regulation of the SRSF1/RBPJ pathway, thereby providing a possible therapeutic target for asthma treatment that warrants further validation.