PAKISTAN VETERINARY JOURNAL

Pak Vet J, 2025, 45(4) 2074-2080

The Role of Glutamate Dehydrogenase 1 in Congenital Obstructive Nephropathy: Insights from Neonatal Rodent Models and Implications for Veterinary Medicine

Rui Wang^{1, 2, #}, Qian Zhao^{1, 2, #}, Xu Fan^{1,
2}, Xilin Gao^{1, 2}, Jianjun Zhang³, Xiaohan Yu^{1, 2}, Shenglai Zhou⁶, Jinpeng Liu⁷, Dongxin Liu⁸，Xiaofeng Gao⁴, Jia You⁵, Xin Liu^{1, 2, *} and Yi Yang^{1, 2, *}

¹Department of Pediatric Urology, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, China; ²Key Laboratory of Health Ministry for Congenital Malformation, Shengjing Hospital of China Medical University, Shenyang 117004, China; ³Department of Gastric Surgery, Liaoning Cancer Hospital & Institute (Cancer Hospital of Dalian University of Technology), Shenyang 110042, China; ⁴Department of Pediatric Urology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong, China; ⁵Department of Urology, Wuhan Children’s Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430016, China; ⁶Department of Laboratory Animal Science, China Medical University, Shenyang 110122, China; ⁷College of Animal Science and Veterinary Medicine, Shenyang Agricultural University, Shenyang110866, China; ⁸Research Center for Swine Diseases, College of Veterinary Medicine, Sichuan Agricultural University，Chengdu 611130, China.

*Corresponding author: liuxinlobo@hotmail.com (XL); yangyilab@163.com (YY)

Abstract

Congenital obstructive nephropathy (CON) refers to kidney damage caused by impaired urine flow due to congenital malformations of the urinary tract. CON is a leading cause of chronic kidney disease (CKD) in young animals, particularly in dogs and cattle, characterized by congenital urinary tract obstruction-induced renal tissue inflammation, fibrosis, and progressive parenchymal damage. It represents a significant clinical challenge in veterinary medicine due to the lack of effective therapeutic options. Glutamate dehydrogenase 1 (GDH1), a key mitochondrial enzyme regulating amino acid metabolism, energy homeostasis, and redox balance, is linked to renal fibrosis via Reactive Oxygen Species (ROS) and profibrotic pathways, making it a plausible target for CON, while the role of GDH1 in animals with CON remains unclear. This study evaluates the role of GDH1 in obstructive renal injury via in vivo and in vitro models. The function of GDH1 was investigated in a neonatal rat model of partial unilateral ureteral obstruction (PUUO) and the potential mechanism was explored in an in vitro model. GDH1 expression was reduced in a neonatal rat model of PUUO. GDH1 overexpression alleviated renal fibrosis in PUUO-operated rats. TGF-β1-treated rat renal tubular epithelial cells (NRK-52E) were employed as an in vitro model. Besides, GDH1 overexpression conferred protection against TGF-β1-induced cellular damage, which was mediated by enhanced cell survival, reduced apoptosis, as well as the suppression of pro-fibrotic marker expression. In conclusion, our study confirms GDH1-mediated protection conferring resistance against CON, highlighting GDH1 as a promising therapeutic target.

To Cite This Article: Wang R, Zhao Q, Fan X, Gao X, Zhang J, Yu X, Zhou S, Liu J, Liu D, Gao X, You J, Liu X and YangY, 2025. The role of glutamate dehydrogenase 1 in congenital obstructive nephropathy: insights from neonatal rodent models and implications for veterinary medicine. Pak Vet J, 45(4): 2074-2080. http://dx.doi.org/10.29261/pakvetj/2025.xxx

Abstract

ISSN 0253-8318 (Print)ISSN 2074-7764 (Online)

ISSN 0253-8318 (Print)
ISSN 2074-7764 (Online)