In:
Journal of Cellular and Molecular Medicine, Wiley, Vol. 19, No. 5 ( 2015-05), p. 1151-1161
Abstract:
Extracellular high‐mobility group box‐1 ( HMGB 1) acts as a signalling molecule during inflammation, cell differentiation and angiogenesis. Increased abundance of HMGB 1 is associated with several pathological disorders such as cancer, asthma and chronic obstructive pulmonary disease ( COPD ). In this study, we investigated the relevance of HMGB 1 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 HMGB 1‐positive cells. Increased HMGB 1 serum levels were detected in both patient populations compared to control samples. The effects of physiological HMGB 1 concentrations were then examined on cellular responses in vitro . HMGB 1 enhanced proliferation of pulmonary arterial smooth muscle cells ( PASMC ) and primary human arterial endothelial cells ( PAEC ). HMGB 1 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 HMGB 1‐induced proliferation in PASMC . Thus, an inflammatory component such as HMGB 1 can contribute to PASMC and PAEC proliferation and therefore potentially to vascular remodelling and PH pathogenesis.
Type of Medium:
Online Resource
ISSN:
1582-1838
,
1582-4934
DOI:
10.1111/jcmm.2015.19.issue-5
Language:
English
Publisher:
Wiley
Publication Date:
2015
detail.hit.zdb_id:
2076114-4
