Bioinformatics data mining approach indicates the expression of chromatin immunoprecipitation followed by deep sequencing (ChIP‐Seq)‐based hypoxia‐inducible factor‐1α target genes in periplaque lesions of multiple sclerosis. Issue 2 (9th February 2015)

• Record Type: Journal Article
• Authors: Satoh, Jun‐ichi; Asahina, Naohiro; Kitano, Shouta; Kino, Yoshihiro
• Is Part Of: Clinical & experimental neuroimmunology. Volume 6:Issue 2(2015)
• Page Start: 159
• Page End: 169
• Publication Date: 2015-02-09
• Subjects: 616.80479
• DOI: 10.1111/cen3.12195
• Languages: English
• ISSNs: 1759-1961

Abstract

<abstract abstract-type="main" id="cen312195-abs-0001"> <title>Abstract</title> <sec id="cen312195-sec-0001" sec-type="section"> <title>Objectives</title> <p>Hypoxia, a hallmark feature of chronic inflammation, plays a key role in the development of inflammatory demyelinating lesions of multiple sclerosis (MS). Periplaque demyelinated lesions (PDL) of MS represent incompletely demyelinated lesions surrounding fully demyelinated plaques, characterized by low‐grade inflammation and tissue remodeling. At present, the precise molecular pathology of PDL remains unknown.</p> </sec> <sec id="cen312195-sec-0002" sec-type="section"> <title>Methods</title> <p>To study the role of hypoxia in the pathophysiology of PDL, we identified a comprehensive set of chromatin immunoprecipitation followed by deep sequencing (ChIP‐Seq)‐based hypoxia‐inducible factor‐1α (HIF‐1α) direct target genes in human umbilical vein endothelial cells by <italic>in silico</italic> next‐generation sequencing data analysis. We characterized HIF‐1α target signature in PDL of secondary progressive MS by analyzing a microarray dataset.</p> </sec> <sec id="cen312195-sec-0003" sec-type="section"> <title>Results</title> <p>We identified a total of 2291 hypoxia‐restricted HIF‐1α target genes. The set of 80 genes (15%) out of 549 upregulated genes in PDL, compared with normal appearing white matter, corresponded to ChIP‐Seq‐based HIF‐1α target genes. They showed a significant relationship with the molecular network composed of the semaphorin Sema6D, a key molecule involved in activation of antigen‐specific T cells by dendritic cells.</p> </sec> <sec id="cen312195-sec-0004" sec-type="section"> <title>Conclusions</title> <p>These results suggest a possible involvement of hypoxia in periplaque lesion formation in MS.</p> </sec> </abstract>