miR34a: a master regulator in the pathogenesis of bronchopulmonary dysplasia
Authors:Pragnya Das1, Mansoor Ali Syed1,2, Dilip Shah1, Vineet Bhandari1,3,*
1 Section of Neonatology, Department of Pediatrics, Drexel University College of Medicine, Philadelphia 19102.
2 Department of Biotechnology, Jamia Millia Islamia, New Delhi, India 110025.
3 St. Christopher’s Hospital for Children, Philadelphia, PA 19134.
Keywords:
miR34a, BPD, hyperoxia, lungs, angiopoietin1, p53, SIRT1, surfactant.
Corresponding Author(s):
Conflict of interest statement:
The authors declare no conflict of interest.
Please cite this article as:
: Pragnya Das, Mansoor Ali Syed Dilip Shah, Vineet Bhandari (2018). miR34a: a master regulator in the pathogenesis of bronchopulmonary dysplasia. Cell Stress 2(2): 34-36. doi: 10.15698/cst2018.02.124
© 2018 Das et al. This is an open-access article released under the terms of the Creative Commons Attribution (CC BY) license, which allows the unrestricted use, distribution, and reproduction in any medium, provided the original author and source are acknowledged.
Abstract:
Bronchopulmonary dysplasia (BPD) is the most common chronic lung disease in infants with lifelong pulmonary and neurodevelopmental consequences. The pathogenesis of BPD is contributed by genetic and environmental factors; among the latter, a critical contributor is exposure of the developing lung to hyperoxia. We have recently reported (Nat Comm 8:1173) that hyperoxia exposure in our in vitro and in vivo modeling systems of hyperoxia-induced lung injury (HALI) and BPD leads to an upregulation of the microRNA (miR) 34a. Utilizing genetic loss- and gain- of function strategies, we show that miR34a inhibition ameliorates the pulmonary phenotype of BPD (including BPD-associated pulmonary hypertension), at least in part, via one of the downstream targets of miR34a, namely Angiopoietin1/Tie 2 signaling. In addition, we demonstrate translational clinical significance of our findings by showing increased miR34a and decreased Ang1 expression in 3 independent cohorts of human lung samples.