Chromatin dynamics via HMGN5 regulates COPD susceptibility

Autor: Michael Bustin, Takashi Furusawa, Rim S.J. Sarker, Julian Dorer, Ali Önder Yildirim, Martin Hrabě de Angelis, Helmut Fuchs, Thomas M. Conlon, Gerald Burgstaller, Lisa Merthan, Valerie Gailus-Durner
Rok vydání: 2020
Předmět:
Zdroj: Molecular pathology and funct. genomics.
Popis: A role for epigenetics in COPD susceptibility is emerging. We previously detected spontaneous emphysema development in HMGN5 deficient mice. HMGN5 binds to the nucleosomal core particle of chromatin, competing with histone H1, thus altering chromatin structure and function. Here we investigate the contribution of HMGN5 to the development of emphysema. COPD patient lungs were analyzed by RNAseq and immunofluorescence. B6 and Hmgn5-/- mice were treated with porcine pancreatic elastase (PPE, 40U/Kg) and analyzed on d28. siRNA knock-down of Hmgn5 in ATII cells (LA4) was followed by wound healing, apoptosis and cell proliferation assays. RNAseq of COPD patients demonstrated a 58% reduction (p This data suggests a novel causal link between chromatin dynamics and emphysema development via increased apoptosis and impaired cell proliferation, highlighting potential new therapeutic avenues for impeding emphysema progression.
Databáze: OpenAIRE