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.