Extracellular Nucleophosmin Is Increased in Psoriasis and Correlates With the Determinants of Cardiovascular Diseases

Frontiers in Cardiovascular Medicine

article

Marco D'Agostino¹  Sara Beji¹  Sara Sileno²  Daniela Lulli¹  Laura Mercurio¹  Stefania Madonna¹  Corrado Cirielli³  Sabatino Pallotta⁴  Cristina Albanesi¹  Maurizio C. Capogrossi⁵  Daniele Avitabile⁷  Guido Melillo⁸  Alessandra Magenta² 

[1] Experimental Immunology Laboratory, Istituto Dermopatico dell'Immacolata;National Research Council of Italy ,(CNR), Institute of Translational Pharmacology;Unit of Vascular Surgery, Istituto Dermopatico dell'Immacolata;Division of Dermatology, Istituto Dermopatico dell'Immacolata;Division of Cardiology, Johns Hopkins Bayview Medical Center, Johns Hopkins University;Laboratory of Cardiovascular Science, National Institute on Aging ,(NIA), National Institutes of Health;Idi Farmaceutici S.r.l.;Unit of Cardiology, Istituto Dermopatico dell'Immacolata

关键词: alarmin;    inflammation;    microRNAs;    psoriasis;    atherosclerosis;    cardiovascular diseases;   

DOI  :  10.3389/fcvm.2022.867813

学科分类：地球科学(综合)

来源: Frontiers

【 摘 要 】

We previously showed that genotoxic stress induced an active extracellular release of nucleophosmin (NPM) in human cardiac mesenchymal progenitor cells, and that serum deprivation provokes NPM secretion from human endothelial cells, eliciting inflammation via nuclear factor kappa B (NF-kB) transcriptional activation. In this study, we wanted to determine whether NPM was similarly modulated in the skin and plasma of psoriatic patients (Pso). We found that NPM was induced in 6 skin biopsies compared to 6 normal skin biopsies and was markedly increased in lesional (LS) vs. non-lesional skin (NLS) biopsies. Moreover, NPM was also increased at the transcriptional levels in LS vs. NLS. Both the innate stimuli, such as lipopolysaccharides and Poly inositol–cytosine and adaptive stimuli, that is, cytokine mix, were able to induce the extracellular release of NPM in immortalized keratinocytes and human skin fibroblasts in the absence of cytotoxicity. Interestingly, NPM interacts with Toll-like receptor (TLR)4 in these cells and activates an NF-kB-dependent inflammatory pathway upregulating interleukin IL-6 and COX-2 gene expression. Finally, circulating NPM was increased in the plasma of 29 Pso compared to 29 healthy controls, and positively correlates with psoriasis area severity index (PASI) and with determinants of cardiovascular diseases (CVDs), such as pulse wave velocity, systolic pressure, and left ventricular mass. Furthermore, NPM positively correlates with miR-200c circulating levels, which we previously showed to increase in Pso and correlate with CVD progression. Our data show that circulating miR-200c is physically associated with extracellular NPM, which most probably is responsible for its extracellular release and protection upon cytokine mix via a TLR4-mechanism. In conclusion, NPM is increased in psoriasis both in the skin and plasma and might be considered a novel biologic target to counteract chronic inflammation associated with CVD risk.

【 授权许可】

CC BY