Significant role and the underly mechanism of cullin-1 in chronic obstructive pulmonary disease

Wenbo Hao; Fei Lin; Weili Kong; Hanbing Shi; Haiying Dong; Zhanjiang Guan; Guohua Liu; Xiao Wang; Li Wang; Moran Liu; Yunfei Jiang

doi:10.1515/med-2024-1070

Significant role and the underly mechanism of cullin-1 in chronic obstructive pulmonary disease

Open Med (Wars). 2024 Nov 18;19(1):20241070. doi: 10.1515/med-2024-1070. eCollection 2024.

Authors

Wenbo Hao¹, Fei Lin², Weili Kong³, Hanbing Shi³, Haiying Dong⁴, Zhanjiang Guan⁵, Guohua Liu³, Xiao Wang³, Li Wang⁶, Moran Liu⁷, Yunfei Jiang⁸

Affiliations

¹ Cardiothoracic Surgery, The Third Affiliated Hospital of Qiqihar Medical University, Qiqihar, 161006, China.
² Endocrinology, The Third Affiliated Hospital of Qiqihar Medical University, Qiqihar, 161006, China.
³ Department of Respiratory and Critical Care Medicine, The Third Affiliated Hospital of Qiqihar Medical University, Qiqihar, 161006, China.
⁴ Pathology and Pathophysiology, Qiqihar Medical University, Qiqihar, 161006, China.
⁵ Intensive Care Unit, The Third Affiliated Hospital of Qiqihar Medical University, Qiqihar, 161006, China.
⁶ Radiology Imaging Diagnosis Center, The Third Affiliated Hospital of Qiqihar Medical University, Qiqihar, 161006, China.
⁷ Test Center, The Third Affiliated Hospital of Qiqihar Medical University, Qiqihar, 161006, China.
⁸ Department of Respiratory and Critical Care Medicine, The Third Affiliated Hospital of Qiqihar Medical University, No. 27 Taishun Street, Tiefeng District, Qiqihar, 161006, China.

Abstract

Background: This study investigated the role and mechanisms of cullin-1 (CUL1) in chronic obstructive pulmonary disease (COPD).

Methods: Cigarette smoke extract (CSE)-treated mouse pulmonary microvascular endothelial cells (mPMECs) and cigarette smoke inhalation (CSI)-stimulated mice were used to construct in vitro and in vivo COPD models, respectively. CUL1 expression was assessed using reverse transcriptase-quantitative polymerase chain reaction, Western blotting, and immunohistochemistry. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and flow cytometry were used to detect cell viability and apoptosis, respectively. We conducted an enzyme-linked immunosorbent assay on mPMECs and bronchoalveolar lavage fluid (BALF) to detect inflammatory factors. Reactive oxygen species, malondialdehyde, and superoxide dismutase were detected using the corresponding kits. The histological characteristics of the lung tissues were determined by hematoxylin and eosin staining.

Results: CUL1 expression was downregulated in COPD. CUL1 overexpression significantly promoted cell viability, reduced cell apoptosis, and inhibited inflammatory responses and oxidative stress in CSE-treated mPMECs. These changes were reversed by the p53 agonist nutlin-3. In addition, CUL1 overexpression significantly relieved COPD in mice, as confirmed by the reduced secretion of inflammatory factors in BALF, inhibited oxidative stress response, and improved lung function.

Conclusion: CUL1 plays a protective role in CSE-treated mPMECs and CSI-stimulated mice by inhibiting the p53 signaling pathway.

Keywords: chronic obstructive pulmonary disease; cigarette smoke extract; cigarette smoke inhalation; cullin-1; p53 pathway.