Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Involvement of YAP and LATS1 in lung development in a rat model of nitrofen-induced congenital diaphragmatic hernia

Junzuo Liao¹, Wenying Liu^1,2 , Libin Zhang¹, Qin Li Li¹, Fang Hou¹

¹Department of Pediatric Surgery, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China; ²Institute of Laboratory Animais of Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu City, China.

For correspondence:- Wenying Liu Email: vpvpe7@163.com

Accepted: 25 February 2020 Published: 31 March 2020

Citation: Liao J, Liu W, Zhang L, Li Q, Hou F. Involvement of YAP and LATS1 in lung development in a rat model of nitrofen-induced congenital diaphragmatic hernia. Trop J Pharm Res 2020; 19(3):541-547 doi: 10.4314/tjpr.v19i3.12

© 2020 The authors.
This is an Open Access article that uses a funding model which does not charge readers or their institutions for access and distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0) and the Budapest Open Access Initiative (http://www.budapestopenaccessinitiative.org/read), which permit unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited..

Abstract

Purpose: To investigate the role of Hippo pathway in lung development in congenital diaphragmatic hernia (CDH).

Methods: One oral dose of nitrofen was maternally administered for induction of CDH on embryonic day 9.5 (E 9.5). Sildenafil was administered intragastrically at a dose of 100 mg/kg on E 11.5. Three rat groups were used: control, CDH, and CDH + sildenafil. Cesarean section was used for fetal delivery on E 21.5. Fetuses with left diaphragmatic hernia (except in control rats) were chosen for investigations. Fetal body weight and weight of lung tissue were recorded, and lung histological evaluation, western blot and PCR were carried out after lung processing.

Results: There was markedly higher expression of YAP in CDH rats than in control rats was unaffected by antenatal sildenafil administration (p < 0.05). However, prenatal sildenafil intervention significantly increased LATS1 expression in the lung of CDH fetuses (p < 0.05).

Conclusion: These results indicate that increased pulmonary YAP expression in CDH rat model might contribute to pulmonary vascular remodeling and suppression of lung development. Thus, antenatal sildenafil administration not only mitigates abnormal vascular remodeling but also promotes lung development, most likely via increased expression of LATS1.

Keywords: Congenital diaphragmatic hernia (CDH), Hippo pathway, Lung development, Sildenafil