1. The PAR6B-PRKCI-PAR3 complex influences alveolar regeneration in patients with the emphysema subtype of chronic obstructive pulmonary disease.
- Author
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Wang, Di, Liu, Hongbo, Bai, Shuang, Zheng, Xuejian, and Zhao, Li
- Abstract
Background: Chronic obstructive pulmonary disease (COPD) is gaining increasing attention, with different subtypes being distinguished for separate research and treatment. The emphysema subtype is characterized by widespread alveolar destruction, which may be associated with aggravated alveolar damage and abnormal repair. Type II alveolar epithelial cells (AEC2s), known for their stem cell potential, have recently emerged as a promising target for COPD treatment. However, to date, few studies have elucidated the specific mechanisms by which AEC2s induce alveolar regeneration. Methods: Lung tissue samples from COPD patients were collected, and bioinformatics analysis was used to identify expression profiles affecting the emphysema phenotype and target genes regulating AEC2 proliferation. In vitro models of smoke-induced injury and viral transfection were established to clarify the role of the target gene PARD6B in regulating AEC2s proliferation and transdifferentiation potential. Co-immunoprecipitation and mass spectrometry were employed to elucidate the specific regulatory mechanisms. Primary mouse AEC2s were isolated for 3D spheroid formation experiments to further validate the role of the target gene. Results: We observed impaired self-proliferation and enhanced transdifferentiation of AEC2s into AEC1s in lung tissues from COPD patients with emphysema subtype, which was associated with reduced expression of PARD6B. Interestingly, PARD6B primarily functioned as part of a complex in AEC2s. Mechanistically, we found that reduced levels of the PAR3-PARD6B-PRKCI complex could arrest the cell cycle of AEC2s in the G0-G1 phase, thereby impairing their self-proliferation. Conclusions: Our findings reveal a novel regulatory mechanism for alveolar regeneration, highlighting a potential therapeutic target for managing the emphysema subtype of COPD. [ABSTRACT FROM AUTHOR]
- Published
- 2025
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