Urantide alleviates the symptoms of atherosclerotic rats in vivo and in vitro models through the JAK2/STAT3 signaling pathway
| Autor: | Tu Wang, Lide Xie, Hongdong Bi, Ying Li, Juan Zhao |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
STAT3 Transcription Factor
0301 basic medicine Vascular smooth muscle Urotensins Primary Cell Culture Muscle Smooth Vascular Stat3 Signaling Pathway Receptors G-Protein-Coupled 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Cell Movement Animals Rats Wistar Receptor STAT3 Aorta Cell Proliferation Pharmacology Janus kinase 2 biology Janus Kinase 2 Atherosclerosis Peptide Fragments Cell biology Lipoproteins LDL Disease Models Animal 030104 developmental biology chemistry biology.protein STAT protein Signal transduction Urotensin-II 030217 neurology & neurosurgery Signal Transduction |
| Zdroj: | European Journal of Pharmacology. 902:174037 |
| ISSN: | 0014-2999 |
| DOI: | 10.1016/j.ejphar.2021.174037 |
| Popis: | Atherosclerosis is the leading cause of human death, and its occurrence and development are related to the urotensin II (UII) and UII receptor (UT) system and the biological function of vascular smooth muscle cells (VSMCs). During atherosclerosis, impaired biological function VSMCs may promote atherosclerotic plaque formation. The Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) pathway is an important mediator of signal transduction; however, the role of this signaling pathway in atherosclerosis and VSMCs remains unknown. This study aimed to investigate the effects of urantide on the JAK2/STAT3 signaling pathway in atherosclerosis. We examined the effect of urantide on the UII/UT system and the JAK2/STAT3 signaling pathway in a high fat diet induced atherosclerosis rat model and studied the effect and mechanism of urantide on the phenotypic transformation of VSMCs. We found that the UII/UT system and JAK2/STAT3 signaling pathway were highly activated in the thoracic aorta in atherosclerotic rats and in ox-LDL- and UII-induced VSMCs. After urantide treatment, the pathological changes in atherosclerotic rats were effectively improved, and the activities of the UII/UT system and JAK2/STAT3 signaling pathway were inhibited. Moreover, urantide effectively inhibited proliferation and migration and reversed the phenotypic transformation of VSMCs. These results demonstrated that urantide may control the JAK2/STAT3 signaling pathway by antagonizing the UII/UT system, thereby maintaining the biological function of VSMCs and potentially preventing and curing atherosclerosis. |
| Databáze: | OpenAIRE |
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