Smooth Muscle Cell Phenotypic Switch Induced by Traditional Cigarette Smoke Condensate: A Holistic Overview
Articolo
Data di Pubblicazione:
2023
Citazione:
Smooth Muscle Cell Phenotypic Switch Induced by Traditional Cigarette Smoke Condensate: A Holistic Overview / L. Bianchi, I. Damiani, S. Castiglioni, A. Carleo, R. De Salvo, C. Rossi, A. Corsini, S. Bellosta. - In: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. - ISSN 1422-0067. - 24:7(2023 Mar), pp. 6431.1-6431.23. [10.3390/ijms24076431]
Abstract:
Cigarette smoke (CS) is a risk factor for inflammatory diseases, such as atherosclerosis.
CS condensate (CSC) contains lipophilic components that may represent a systemic cardiac risk
factor. To better understand CSC effects, we incubated mouse and human aortic smooth muscle cells
(SMCs) with CSC. We evaluated specific markers for contractile [i.e., actin, aortic smooth muscle
(ACTA2), calponin-1 (CNN1), the Kruppel-like factor 4 (KLF4), and myocardin (MYOCD) genes] and
inflammatory [i.e., IL-1 , and IL-6, IL-8, and galectin-3 (LGALS-3) genes] phenotypes. CSC increased
the expression of inflammatory markers and reduced the contractile ones in both cell types, with KLF4
modulating the SMC phenotypic switch. Next, we performed a mass spectrometry-based differential
proteomic approach on human SMCs and could show 11 proteins were significantly affected by
exposition to CSC (FC 2.7, p 0.05). These proteins are active in signaling pathways related
to expression of pro-inflammatory cytokines and IFN, inflammasome assembly and activation, cytoskeleton
regulation and SMC contraction, mitochondrial integrity and cellular response to oxidative
stress, proteostasis control via ubiquitination, and cell proliferation and epithelial-to-mesenchymal
transition. Through specific bioinformatics resources, we showed their tight functional correlation
in a close interaction niche mainly orchestrated by the interferon-induced double-stranded RNAactivated
protein kinase (alternative name: protein kinase RNA-activated; PKR) (EIF2AK2/PKR).
Finally, by combining gene expression and protein abundance data we obtained a hybrid network
showing reciprocal integration of the CSC-deregulated factors and indicating KLF4 and PKR as the
most relevant factors.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
atherosclerosis; cigarette smoke; KLF4; MYOCD; EIF2AK2/PKR; phenotypic switch; smooth muscle cells
Elenco autori:
L. Bianchi, I. Damiani, S. Castiglioni, A. Carleo, R. De Salvo, C. Rossi, A. Corsini, S. Bellosta
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