| Summary: | Introduction
Cigarette smoking may impact the progression of idiopathic pulmonary
fibrosis (IPF), and the intensity of smoking presents a dose-response association
with IPF.
Methods
We retrospectively analyzed IPF patients diagnosed in our hospital from
2014 to 2018 and performed follow-up to confirm survival status and duration,
and determine the effect of smoking on the prognosis of IPF. We retrieved
information on IPF from a bioinformatics database to identify the differential
expression of lncRNAs and proteins in smokers. Therefore, we explored and
verified the mechanism by which cigarette smoke exposure (CSE) regulates
LINC00665/XBP-1 involvement in pulmonary fibrosis through cell experiments.
We clarified the mechanism between LINC00665 and XBP-1 through cellular and
molecular experiments, and verified the inhibitory effect of silencing LINC00665
on pulmonary fibrosis by using a bleomycin (BLM)-induced pulmonary fibrosis
model.
Results
We found that smokers with IPF had a poor prognosis compared with
non-smokers. Both the expression of LINC00665 and XBP-1 in IPF lung tissue
and smoker lung tissue were significantly upregulated, moreover, LINC00665
was higher in smoker IPF lung tissue than in smoker healthy people. Exposure
to CSE could upregulate LINC00665/XBP-1 in lung fibroblast-to-myofibroblast
transition. Cellular and molecular experiments showed that LINC00665 regulates
the expression of XBP-1 by targeting miR-214-3p. LINC00665 expression, was
significantly upregulated in BLM-induced mouse lung fibrosis tissues, and
LINC00665 knockdown inhibited fibrogenesis in BLM-induced lung fibrosis.
Conclusions
Our study found that the high expression of LINC00665 is involved in
the pathogenesis of smoker IPF and that CSE may positively regulate LINC00665/
XBP-1 to participate in lung fibroblast-to-myofibroblast transition. These
findings help elucidate the pathogenesis of smoker IPF and may contribute to
the development of new targeted drugs for IPF therapy.
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