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

Junzuo Liao,Libin Zhang,Qin Li,Fang Hou,Wenying Liu,L Yang,Z Xu

doi:10.1051/e3sconf/202018503003

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.

Highlights

Congenital diaphragmatic hernia (CDH) is a significant clinical problem, occurring once in every 2500 human births
We determined the incidence of CDH in the two groups: none of the 76 fetuses in the control group presented with CDH and 49 out of 72 fetuses (68.6%) presented with CDH in the CDH group
Due to ethical and technical constraints, animal models have become an indispensable tool for the study of congenital diaphragmatic hernia

Summary

Introduction

Congenital diaphragmatic hernia (CDH) is a significant clinical problem, occurring once in every 2500 human births. Vascular remodeling is an important pathologic process in the development of many cardiovascular diseases, such as pulmonary hypertension, involving cell growth, death, migration, and synthesis and degradation of extracellular matrix[1]. Hippo signaling pathway plays an important role in determining organ size and maintaining tissue homeostasis. YAP is one of the main effector molecules of this signaling pathway and is closely related to cell growth, proliferation and apoptosis. With the development of research, more and more studies showed that this pathway was closely related to the vascular remodeling. It had been reported that there was a positive feedback mechanism between miR-130a and YAP, which could make YAP activated continuously, and its function may be related to abnormal organ enlargement, tumorigenesis and the formation of persistent pulmonary hypertension[2]

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