2.4 Asthma
Asthma is one of the most prevalent chronic inflammatory diseases, typically characterized by airway hyperresponsiveness and airway obstruction, and nonspecific airway symptoms caused by specific triggers (such as allergens, environmental factors, infections, etc.). Airway remodeling, including thickening of the airway wall and narrowing of the airway, can occur in younger children as a result of epithelial injury, cilia failure, cupular cell proliferation, fibroblasts, and growth of airway smooth muscle cells[89]. For now, there are approximately 300 million asthma patients worldwide[90]. Over the last 40 years, there has been a significant surge on the prevalence, morbidity and mortality associated with asthma among children[91].
Through its association with miR-124, lnc-NEAT1 triggers the release of a number of inflammatory cytokines, and it is linked to a high risk of severe asthma exacerbations [92]. Besides this, lnc PVT1 suppresses the expression of miR-149, increases inflammation in small airway epithelial cells, and impairs cellular defense barrier function[93]. Asthma-related lung inflammation is mediated by CD4+ T cells, and asthma development is facilitated by enhanced T cell differentiation of Th2 cells. Asthma-induced lung inflammation is amplified as lnc MALAT1 competitively binds miR-155 with CTLA-4 through a ceRNA mechanism. This can boost CTLA-4 expression, which in turn causes up- and down-regulation of the essential Th1/Th2 transcription regulators T-bet and GATA3[94].
Airway smooth muscle cells (ASM) are the primary effector cells in asthma, and several studies have revealed that ASM cells proliferate in asthma patients and promote a more contractile ASM phenotype in response to inflammatory factor stimulation[95]. The upstream lnc NEAT1 was identified to modulate SLC26A2 expression by targeting miR-9-5p, enhance ASM cell proliferation, migration, contraction, and boost inflammation in child asthma patients[96].
Platelet-derived growth factor BB (PDGF-BB) stimulates Malat1 expression in airway smooth muscle cells, Malat1 interacts with miR-150 by a ceRNA mechanism, significantly enhances the essential translation initiation factor, eIF4E, and Akt signaling, promotes airway smooth muscle cells proliferation and migration, airway remodeling in asthma[97]. Meanwhile, there are studies demonstrated that lnc GAS5 acts on miR-10a/BDNF axis[98], lnc PVT1 acts on miR-590-5p/FSTL1 axis[99], lnc Malat1 acts on miR-150-eIF4E/AKT axis[100] influencing ASM cell proliferation and migration in asthma.