Convergent transcriptional regulatory networks in diseases such as chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF) may have shared responses in the lung to environmental stresses, according to data published in the American Journal of Respiratory and Critical Care Medicine.
COPD and IPF are typically studied separately, but these diseases share similar environmental exposures. Therefore, Avrum Spira, MD, from Boston University School of Medicine and Naftali Kaminski, MD, from Yale School of Medicine, and colleagues used RNA sequencing to define the transcriptional repertoire of COPD, IPF, or normal histology lungs (n=87) to identify convergent transcriptomic pathways in emphysema and IPF.
Gene expression arrays showed that genes increased in emphysema and IPF were enriched for the p53/hypoxia pathway compared with controls (n=193). In tissues from patients with emphysema or IPF, the researchers observed overexpression of H1F1A, MDM2, and NFKBIB members of this pathway.
The investigators also determined that alternative splicing of p53/hypoxia pathway-associated molecules NUMB and PDGFA occurred more often in emphysema or IPF compared with the controls. The findings were validated with quantitative polymerase chain reaction and the nCounter Analysis System on an independent sample set (n=193).
- Kusko RL, Brothers JF, Tedrow J, et al. Integrated genomics reveals convergent transcriptomic networks underlying chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2016; doi: 10.1164/rccm.201510-2026OC.