Contrasting effects of intracellular and extracellular human PCSK9 on inflammation, lipid alteration and cell death.
Aram GhalaliFahd AlhamdanSwapna UpadhyayKoustav GangulyKjell LarssonLena PalmbergMizanur RahmanPublished in: Communications biology (2024)
Proprotein convertase subtilisin/kexin type 9 (PCSK9) is one of the major regulators of low-density lipoprotein receptor (LDLR). Information on role and regulation of PCSK9 in lung is very limited. Our study focuses on understanding the role and regulation of PCSK9 in the lung. PCSK9 levels are higher in Bronchoalveolar lavage fluid (BALF) of smokers with or without chronic obstructive pulmonary diseases (COPD) compared to BALF of nonsmokers. PCSK9-stimulated cells induce proinflammatory cytokines and activation of MAPKp38. PCSK9 transcripts are highly expressed in healthy individuals compared to COPD, pulmonary fibrosis or pulmonary systemic sclerosis. Cigarette smoke extract reduce PCSK9 levels in undifferentiated pulmonary bronchial epithelial cells (PBEC) but induce in differentiated PBEC. PCSK9 inhibition affect biological pathways, induces lipid peroxidation, and higher level of apoptosis in response to staurosporine. Our results suggest that higher levels of PCSK9 in BALF acts as an inflammatory marker. Furthermore, extracellular and intracellular PCSK9 play different roles.
Keyphrases
- low density lipoprotein
- systemic sclerosis
- cell death
- oxidative stress
- cell cycle arrest
- chronic obstructive pulmonary disease
- pulmonary hypertension
- interstitial lung disease
- endothelial cells
- endoplasmic reticulum stress
- induced apoptosis
- transcription factor
- smoking cessation
- healthcare
- cell proliferation
- health information
- air pollution
- binding protein
- induced pluripotent stem cells
- social media