Urotensin receptor antagonist urantide improves atherosclerosis-related kidney injury by inhibiting JAK2/STAT3 signaling pathway in rats
| Autor: | Tu Wang, Ya-Qin Xie, Guang-Xin Miao, Hai-peng Cui, Kai Liu, Ying Li, Juan Zhao |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
MAPK/ERK pathway Male STAT3 Transcription Factor medicine.medical_specialty MAP Kinase Signaling System Urotensins Kidney 030226 pharmacology & pharmacy General Biochemistry Genetics and Molecular Biology Stat3 Signaling Pathway Nephropathy Receptors G-Protein-Coupled 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Internal medicine medicine Animals General Pharmacology Toxicology and Pharmaceutics Rats Wistar Receptor NOX4 General Medicine Janus Kinase 2 medicine.disease Atherosclerosis Peptide Fragments Rats 030104 developmental biology Endocrinology medicine.anatomical_structure chemistry Gene Expression Regulation Kidney Diseases Signal transduction Urotensin-II |
| Zdroj: | Life sciences. 247 |
| ISSN: | 1879-0631 |
| Popis: | Objective To investigate the role of urantide in the prevention and treatment of atherosclerotic nephropathy by antagonizing the urotensin II/urotensin receptor (UII/UT) system and regulating JAK2/STAT3 signaling pathway. Methods Atherosclerosis (AS) rats were treated with urantide at a concentration of 30 μg/kg for 3, 7, 14 days. Results An excessive expression of UII and its receptor G protein-coupled receptor 14 (GPR14) was seen in AS rat kidneys and the expression was significantly reduced after urantide administration. Either body weight, renal functions of urea nitrogen, urine proteins and anion gaps or expression of kidney injury-related genes Agtr1α, Nox4, Cyba and Ncf1 were improved after AS rats were treated with urantide. After antagonizing the UII/GPR14 system by using urantide, the expression of genes and proteins in the JAK2/STAT3 and ERK pathways was decreased, and the nuclear protein p-STAT3 and p-ERK were obviously decreased. p-JAK2 and p-STAT3 were decreased in the urantide group in a time-dependent manner. The UII/GPR14 system and JAK2/STAT3 signals were localized in tubules and then glomeruli to affect renal reabsorption and filtration. Conclusion Urantide can effectively block the UII/GPR14 system by regulating the JAK2/STAT3 signaling pathway to prevent and treat atherosclerosis-related kidney injury. At this stage, effective inhibition of inflammatory signaling pathways is of great significance in the treatment of atherosclerosis. |
| Databáze: | OpenAIRE |
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