PT  - JOURNAL ARTICLE
AU  - Lisa Merthan
AU  - Michael Bustin
AU  - Oliver Eickelberg
AU  - Ali Oender Yildirim
TI  - Reduction of high mobility group nucleosome binding domain-5 protein promotes the development of emphysema
DP  - 2014 Sep 01
TA  - European Respiratory Journal
PG  - P1840
VI  - 44
IP  - Suppl 58
4099  - http://erj.ersjournals.com/content/44/Suppl_58/P1840.short
4100  - http://erj.ersjournals.com/content/44/Suppl_58/P1840.full
SO  - Eur Respir J2014 Sep 01; 44
AB  - Chronic obstructive pulmonary disease (COPD) is characterized by airflow limitation which is associated with an enhanced chronic inflammation and development of emphysema. However, the mechanism by which genetic alteration contributes to empyhsema development is still barely understood. In a previous study we have detected spontaneous emphysema development in HMGN5 knockout mice (Kluger E.J., et. al., JBC 2013). The HMGN5 gene encodes a nucleosomal binding protein that competes with H1 on the nucleosome and loosens the structure of chromatin. It plays an important role in transcription, replication and the repair mechanism. We suggest that HMGN5 plays a role during the development of emphysema and investigate this in vitro and in vivo.Porcine pancreas elastase (PPE) treated mice after days 28 and 56 were analyzed for HMGN5 expression at mRNA level by qPCR and for protein by immunohistochemistry. In vitro HMGN5 siRNA was transfected in murine LA-4 (AE2-like) cells with a concentration of 50nM and cell proliferation analyzed by WST-Assay.The PPE treated mice show a time dependent significant down regulation of HMGN5 expression and localization compared to PBS treated control mice. Furthermore, we could confirm that HMGN5 knockout mice demonstrate a progressive airspace enlargement compared to WT animals. Reduction of HMGN5 expression using siRNA revealed a significant downregulation of cell proliferation after 72h.These observations suggest that HMGN5 contributes to emphysema development via impaired cell proliferation and provides a new target for therapeutic intervention in emphysema therapy.