In the U.S., bronchopulmonary dysplasia (BPD) is a chronic lung disease which affects nearly 15,000 premature infants each year. Inhibition of the micro-RNA miR-34a significantly reduced bronchopulmonary dysplasia (BPD) in mice; in a study conducted by Drexel University researchers. Targeting miR-34a, the master regulator could aid in treating the complex disorder. The study was published in Nature Communications.
Supplemental oxygen provided to premature infants with underdeveloped lungs can lead to inflammation and injury in the lungs, and in turn, causes life-long breathing problems like BPD.
It was suspected that the micro-RNA, miR-34a, could play a role in BPD. In earlier studies, it was found that the micro-RNA molecule controls pathways related to inflammation, vascular development, cell death, and cell proliferation. These four major aspects of the disease were controlled by the molecule.
Vineet Bhandari, a faculty member in the Department of Pediatrics at Drexel University's College of Medicine and chief of Neonatal Medicine at St. Christopher's Hospital for Children and colleagues investigated the lung secretion samples obtained from a cohort of premature babies. They found that miR-34a was significantly elevated in the samples taken from infants who eventually developed BPD.
The lung tissue of the babies who died from lung disease was examined postmortem by the researchers. They found that miR-34a was expressed in these samples. Besides, this the production of downstream proteins was suppressed in infants with BPD.
In further research, the investigators found that the levels of miR-34a levels were raised in the lungs of the neonatal mice exposed to high levels of oxygen. When this micro-RNA was blocked by repressing gene expression or by injecting the mice with the downstream target of the miR-34a (angiopoietin-1), lung function improved by 90% compared to controls.
Finding a master regulator involved in BPD was thought to be difficult due to the complexity of the disease. However, the miR-34a was found to control four different pathways involved in BPD, said Bhandari.
The researchers aim at finding new targets to treat BPD and moving toward clinical trials to test these new treatments.