CSE regulates LINC000665/XBP-1 in the progress of pulmonary fibrosis

Min Song; Qinxue Shen; Xiaoli Ouyang; Zijing Zhou; Hong Luo; Hong Peng

doi:10.18332/tid/175004

CSE regulates LINC000665/XBP-1 in the progress of pulmonary fibrosis

Tob Induc Dis. 2023 Dec 18:21:170. doi: 10.18332/tid/175004. eCollection 2023.

Authors

Min Song^{1

2

3

4}, Qinxue Shen^{1

2

3

4}, Xiaoli Ouyang^{1

2

3

4}, Zijing Zhou^{1

2

3

4}, Hong Luo^{1

2

3

4}, Hong Peng^{1

2

3

4}

Affiliations

¹ Department of Pulmonary and Critical Care Medicine, The Second Xiangya Hospital, Central-South University, Changsha, China.
² Research Unit of Respiratory Disease, Central-South University, Changsha, China.
³ Clinical Medical Research Center for Pulmonary and Critical Care Medicine in Hunan Province, Changsha, China.
⁴ Diagnosis and Treatment Center of Respiratory Disease, Central South University, Changsha, China.

Abstract

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.

Keywords: XBP-1; cigarette smoke exposure; lncRNA LINC00665; pulmonary fibrosis; smoking.