High‐mobility group box‐1 induces vascular remodelling processes via c‐Jun activation

Journal of Cellular and Molecular Medicine

Diana Zabini²  Slaven Crnkovic²  Hui Xu³  Maria Tscherner²  Bahil Ghanim²  Walter Klepetko¹  Andrea Olschewski²  Grazyna Kwapiszewska² 

[1] Division of Thoracic Surgery, Department of Surgery, Medical University of Vienna, Vienna, Austria;Ludwig Boltzmann Institute for Lung Vascular Research, Graz, Austria;Experimental Anaesthesiology, Department of Anaesthesia and Intensive Care Medicine, Medical University of Graz, Graz, Austria

关键词: alarmins;    HMGB1;    inflammation;    proliferation;    pulmonary hypertension;   

DOI  :  10.1111/jcmm.12519

来源: Wiley

【 摘 要 】

Abstract

Extracellular high-mobility group box-1 (HMGB1) acts as a signalling molecule during inflammation, cell differentiation and angiogenesis. Increased abundance of HMGB1 is associated with several pathological disorders such as cancer, asthma and chronic obstructive pulmonary disease (COPD). In this study, we investigated the relevance of HMGB1 in the pathological remodelling present in patients with idiopathic pulmonary arterial hypertension (IPAH) and pulmonary hypertension (PH) associated with COPD. Remodelled vessels present in COPD with PH and IPAH lung samples were often surrounded by HMGB1-positive cells. Increased HMGB1 serum levels were detected in both patient populations compared to control samples. The effects of physiological HMGB1 concentrations were then examined on cellular responses in vitro. HMGB1 enhanced proliferation of pulmonary arterial smooth muscle cells (PASMC) and primary human arterial endothelial cells (PAEC). HMGB1 stimulated p38, extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) phosphorylation. Furthermore, activation of the downstream AP-1 complex proteins c-Fos and c-Jun was observed. Silencing of c-Jun ablated the HMGB1-induced proliferation in PASMC. Thus, an inflammatory component such as HMGB1 can contribute to PASMC and PAEC proliferation and therefore potentially to vascular remodelling and PH pathogenesis.

【 授权许可】

CC BY   
© 2015 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

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