LncR-GAS5 decrease in adenine phosphoribosyltransferase expresssion via binding TAF1 to increase kidney damage created by CIH
Wei Liu,
Wukaiyang Liang,
CunTai Zhang,
Huiguo Liu,
Hai Li,
Lun Zhou,
Ling Zhou
Affiliations
Wei Liu
Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, China; Key Laboratory of Vascular Aging, Ministry of Education, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, China
Wukaiyang Liang
Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, China; Key Laboratory of Vascular Aging, Ministry of Education, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, China
CunTai Zhang
Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, China; Key Laboratory of Vascular Aging, Ministry of Education, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, China
Huiguo Liu
Department of Respiratory and Critical Care Medicine, Key Laboratory of Pulmonary Diseases of Health Ministry, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
Hai Li
Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, China; Key Laboratory of Vascular Aging, Ministry of Education, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, China
Lun Zhou
Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, China; Key Laboratory of Vascular Aging, Ministry of Education, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, China; Corresponding author. Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, China.
Ling Zhou
Department of Respiratory and Critical Care Medicine, Key Laboratory of Pulmonary Diseases of Health Ministry, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China; Corresponding author. Department of Respiratory and Critical Care Medicine, Key Laboratory of Pulmonary Diseases of Health Ministry, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China
Objective: Chronic kidney disease (CKD) related to obstructive sleep apnea-hypopnea syndrome (OSAHS) mainly results from chronic intermittent hypoxia (CIH)-induced renal injury. This study aimed to explore the interaction between the long noncoding RNA (lncRNA) growth arrest-specific transcript 5 (GAS5) and recombinant adenine phosphoribosyltransferase (APRT) in CIH-induced renal injury. Methods: A rat intermittent hypoxia model was constructed, total RNA was extracted from kidney tissue, and transcriptome sequencing was performed using high-throughput sequencing technology. CIH rat models were established and injected with sh-GAS5 or OE-APRT plasmid, the serum levels of blood urea nitrogen (BUN) and creatinine amidohydrolase were measured, and the expression of oxidative stress-related factors was detected. Hematoxylin and eosin (H&E) and Masson's trichrome staining were used for morphological observations, and cell apoptosis was determined by TUNEL staining. Interactions between GAS5, TATA-box binding protein-associated factor 1 (TAF1), and APRT were predicted and verified. After transfection of HK-2 cells, the expression of GAS5, TAF1, APRT, Bax, Bcl-2, apoptosis-related factors, fibrosis-related factors (collagen I and Ⅳ), and autophagy-related proteins (LC3-Ⅱ, LC3-Ⅰ, p62, and Beclin-1) was measured by RT-qPCR and western blotting. Results: Sequencing results revealed that TAF1 was significantly increased and APRT was significantly decreased in the CIH group. RNA was significantly involved in the biological process of kidney injury mediated by CIH. CIH rats injected with GAS5 suppression or APRT overexpression plasmids showed decreased GAS5 and elevated APRT expression, along with suppressed serum levels of BUN and creatinine amidohydrolase. Meanwhile, GAS5 suppression or APRT overexpression attenuated apoptosis and fibrosis, suppressed oxidative stress, and promoted autophagy in CIH-induced renal tubular epithelial cells. The RNA pull-down assay and RIP verified the binding and interaction of GAS5 and TAF1. Chip immunoprecipitation (ChIP) identified TAF1 regulation of the APRT promoter. GAS5 and TAF1 negatively regulated APRT expression. Conclusion: The lncRNA GAS5 can bind TAF1 to suppress APRT transcription, thereby enhancing CIH-induced renal injury in rats.
