CYP1B1 Mediates Cigarette Smoke-Induced Lipid Accumulation in Alveolar Type 2 Cells

Authors

Yin Zhu
Siddhika Gamare
Francesca Polverino
Caroline A Owen
Payaningal R Somanath
Xiaoyun Wang
Duo Zhang

Language

English

Publication Date

9-30-2025

Journal

The FASEB Journal

DOI

10.1096/fj.202501439RR

PMID

40971194

PMCID

PMC12448152

PubMedCentral® Posted Date

9-19-2025

PubMedCentral® Full Text Version

Post-print

Abstract

Alterations in lipid profiles have been shown in patients with chronic obstructive pulmonary disease (COPD), but the underlying molecular mechanisms remain unclear. In this study, we aimed to investigate the role of cytochrome P450 family-1 subfamily B member 1 (CYP1B1) in cigarette smoke (CS)-induced lipid accumulation in alveolar type II epithelial (AT2) cells. We observed a steady increase in CYP1B1 protein levels in AT2 cells from COPD patients. Additionally, CS exposure induced CYP1B1 expression in AT2 cells of murine lungs. In vitro, treatment with cigarette smoke extract (CSE) not only upregulated CYP1B1 expression but also triggered lipid accumulation in AT2-like cells. Functionally, overexpression of CYP1B1 promoted lipid accumulation in A549 and MLE-12 cells. Consistently, siRNA-mediated CYP1B1 inhibition significantly reduced CSE-induced lipid accumulation in AT2-like cells. Furthermore, treatment with 2,3',4,5'-tetramethoxystilbene (TMS), a selective CYP1B1 inhibitor, reduced CSE-induced lipid accumulation. TMS also attenuated CSE-induced mitochondrial reactive oxygen species production and cell apoptosis. Taken together, our findings suggest that CYP1B1 is upregulated by CS exposure and plays a key role in CS-induced lipid accumulation in AT2 cells. Targeting CYP1B1 may offer a potential therapeutic strategy for addressing lipid dysregulation and lung pathology in patients with COPD.

Keywords

Cytochrome P-450 CYP1B1, Humans, Animals, Mice, Pulmonary Disease, Chronic Obstructive, Alveolar Epithelial Cells, Lipid Metabolism, Reactive Oxygen Species, Smoke, Apoptosis, Male, Mice, Inbred C57BL, Cigarette Smoking, A549 Cells, Smoking, COPD, e‐cigarettes, lipid metabolism, lung epithelial cell, oxidative stress

Published Open-Access

yes

Recommended Citation

Zhu, Yin; Gamare, Siddhika; Polverino, Francesca; et al., "CYP1B1 Mediates Cigarette Smoke-Induced Lipid Accumulation in Alveolar Type 2 Cells" (2025). Faculty and Staff Publications. 4800.
https://digitalcommons.library.tmc.edu/baylor_docs/4800