The Third Man: DNA sensing as espionage in pulmonary vascular health and disease.
Andrew J BryantAnn PhamHimanshu GogoiCarly R MitchellFaye PaisLei JinPublished in: Pulmonary circulation (2021)
For as long as nucleic acids have been utilized to vertically and horizontally transfer genetic material, living organisms have had to develop methods of recognizing cytosolic DNA as either pathogenic (microbial invasion) or physiologic (mitosis and cellular proliferation). Derangement in key signaling molecules involved in these pathways of DNA sensing result in a family of diseases labeled interferonopathies. An interferonopathy, characterized by constitutive expression of type I interferons, ultimately manifests as severe autoimmune disease at a young age. Afflicted patients present with a constellation of immune-mediated conditions, including primary lung manifestations such as pulmonary fibrosis and pulmonary hypertension. The latter condition is especially interesting in light of the known role that DNA damage plays in a variety of types of inherited and induced pulmonary hypertension, with free DNA detection elevated in the circulation of affected individuals. While little is known regarding the role of cytosolic DNA sensing in development of pulmonary vascular disease, exciting new research in the related fields of immunology and oncology potentially sheds light on future areas of fruitful exploration. As such, the goal of this review is to summarize the state of the field of nucleic acid sensing, extrapolating common shared pathways that parallel our knowledge of pulmonary hypertension, in a molecular and cell-specific manner. Principles of DNA sensing related to known pulmonary injury inducing stimuli are also evaluated, in addition to potential therapeutic targets. Finally, future directions in pulmonary hypertension research and treatments will be briefly discussed.
Keyphrases
- pulmonary hypertension
- nucleic acid
- circulating tumor
- pulmonary artery
- single molecule
- cell free
- pulmonary arterial hypertension
- dna damage
- healthcare
- stem cells
- public health
- multiple sclerosis
- end stage renal disease
- poor prognosis
- signaling pathway
- palliative care
- gene expression
- oxidative stress
- drug induced
- chronic kidney disease
- ejection fraction
- current status
- computed tomography
- human health
- genome wide
- peritoneal dialysis
- long non coding rna
- patient reported outcomes
- real time pcr
- high glucose
- dna methylation
- early onset
- positron emission tomography