Hyperoxia-Induced miR-195 Causes Bronchopulmonary Dysplasia in Neonatal Mice

被引:0
|
作者
Philpot, Patrick [1 ,2 ]
Graumuller, Fred [3 ]
Melchiorre, Nicole [3 ]
Prahaladan, Varsha [2 ,3 ]
Takada, Xander [3 ]
Chandran, Srinarmadha [3 ]
Guillermo, Melissa [3 ]
Dickler, David [3 ]
Aghai, Zubair H. [1 ]
Das, Pragnya [2 ,3 ]
Bhandari, Vineet [2 ,3 ]
机构
[1] Thomas Jefferson Univ, Dept Pediat, Div Neonatol, Nemours, Philadelphia, PA 19107 USA
[2] Drexel Univ, Coll Med, Dept Pediat, Div Neonatol, Philadelphia, PA 19102 USA
[3] Rowan Univ, Childrens Reg Hosp Cooper, Cooper Med Sch, Div Neonatol, Camden, NJ 08103 USA
关键词
lung injury; preterm newborn; chronic lung disease; premature infant; microRNA; targeted therapy; OXIDATIVE STRESS; ANIMAL-MODELS; EXPRESSION; INJURY; AKT; P53;
D O I
10.3390/biomedicines12061208
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Background: Exposure to hyperoxia is an important factor in the development of bronchopulmonary dysplasia (BPD) in preterm newborns. MicroRNAs (miRs) have been implicated in the pathogenesis of BPD and provide a potential therapeutic target. Methods: This study was conducted utilizing a postnatal animal model of experimental hyperoxia-induced murine BPD to investigate the expression and function of miR-195 as well as its molecular signaling targets within developing mouse lung tissue. Results: miR-195 expression levels increased in response to hyperoxia in male and female lungs, with the most significant elevation occurring in 40% O2 (mild) and 60% O2 (moderate) BPD. The inhibition of miR-195 improved pulmonary morphology in the hyperoxia-induced BPD model in male and female mice with females showing more resistance to injury and better recovery of alveolar chord length, septal thickness, and radial alveolar count. Additionally, we reveal miR-195-dependent signaling pathways involved in BPD and identify PH domain leucine-rich repeat protein phosphatase 2 (PHLPP2) as a novel specific target protein of miR-195. Conclusions: Our data demonstrate that high levels of miR-195 in neonatal lungs cause the exacerbation of hyperoxia-induced experimental BPD while its inhibition results in amelioration. This finding suggests a therapeutic potential of miR-195 inhibition in preventing BPD.
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页数:16
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