2.6 pulmonary fibrosis
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive
interstitial lung disease mainly occurs in the elderly. It has a poor
prognosis, a high mortality rate, and prone to acute exacerbation to
respiratory failure[109]. Its etiology is still unknown, however, is
frequently associated with smoking, occupational exposure, air
pollution, and infection. Damage and repair of alveolar epithelial cells
owing to numerous causes, activation of fibroblasts, stimulation of
fibropathic proliferation, recruitment and proliferation of immune cells
such as alveolar macrophages and lymphocytes, and modulation of the
fibrotic response [110], gradual destruction of the normal structure
of the lung, and progressive decompensation of lung function IPF can’t
be reversed or stopped once it starts, although a number of medications
now used to treat it can only slow its advancement[111].
The epithelial-mesenchymal transition (EMT) is critical in the
advancement of pulmonary fibrosis since epithelial cells able
to de-differentiate then differentiate into mesenchymal cells, which
continually produce and accumulate extracellular matrix, directly tied
to signaling pathways such as TGF-1, Smad, and ERK/MAP [112].
Silicosis is caused by long-term silica inhalation and deposition in the
lungs, which leads to diffuse pulmonary fibrosis. Macrophages are
prompted to release TGF-1, which causes lnc ATB expression in epithelial
cells and binds to miR-200c to increase ZEB1 expression in
silica-induced silicosis pulmonary fibrosis [113]. In addition,
miR-29b-2-5p and miR-34c-3p are targets for sponging binding downstream
of lnc ATB, upregulating the expression of MEKK2 and NOTCH2, enabling
lnc ATB to contribute to the acceleration of the EMT process [114].
Lung epithelial cells express more proliferation and EMT-related genes
when lnc NEAT1 interacts with miR-29c [115]. lnc RFAL binds to
miR-18a and activates fibroblasts via CTGF to accelerate the process of
lung fibrosis [116], lnc RFAL also suppresses miR-26a expression,
therefore inhibiting miR-26a’s anti-fibrotic action. A mutually
inhibitory feedback loop established between miR-26a and Smad2,
leads lnc PFRL to increase fibroblast proliferation and transform into
myofibroblast [117].
Liu et al. reported that in silica-induced lung fibrosis in mice
fibroblasts, the overexpression of lnc PCAT29 elevated
miR-221 expression, inhibited TGF-β1 in lung fibroblasts, and slowed the
lung fibrosis process through the RASAL1/ERK1/2 signaling
pathway [118].Through the miR-326/SP1 axis, lnc SNHG1 enhances
fibroblast migration, invasion, and fibrogenic molecule production
[119], whereas lnc SHNG6 promotes fibroblast activation and collagen
accumulation via the miR-26a-5p/TGF-1-smads axis, inducing lung fibrosis
in mice [120].