Overexpression of YAP and miR-130a is closely related to pulmonary hypertension in congenital diaphragmatic hernia

Abstract

Purpose: The aim of this study was to investigate the expression of YAP and miR-130a in the normal lung tissues and CDH lung tissues through the rat model of CDH, and preliminarily explored the relationship between YAP, miR-130a and CDH. Methods: Pregnant rats were divided into two groups: control (n = 5) and CDH (n = 5). A single oral dose (125 mg/kg) of nitrofen was administered to pregnant rats on embryonic day (E) 9.5 to induce CDH. All fetuses were acquired by cesarean delivery on E21.5. Fetuses with diaphragmatic hernias in the CDH groups were chosen for analysis. Lung weight (LW) and body weight (BW) were recorded and histologic evaluations, image analysis, western blot analysis and PCR were performed after lung processing. Results: Five female rats in the control group produced 76 fetuses without CDH. CDH was observed in 49 of 72 rat fetuses in the CDH group. Pulmonary hypoplasia and vascular remodeling were observed in the CDH group. YAP expression in the lungs was markedly increased in the CDH group compared to the control group (P = 0.001). However, there was no significant difference in the phosphorylation level of YAP (P = 0.113) between the two group. YAP mRNA and miR-130a expression in the lungs were markedly increased in the CDH group compared to the control group (P = 0.01, P = 0.002). Conclusion: A relative increase YAP activity and miR-130a expression in the CDH rats may be associated with increased pulmonary vascular resistance. The role of the feedback mechanism between YAP and miR-130a playing in the CDH-associated pulmonary hypertension deserves further study.