Angiotensin II Causes Biphasic STAT3 Activation Through TLR4 to Initiate Cardiac Remodeling
| Autor: | Shiju Ye, Liqin Jiang, Weijian Huang, Taiwei Chen, Chunpeng Zou, Jieli Li, Yi Wang, Jianjiang Xu, Jibo Han, Guang Liang, Jingying Wang |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
STAT3 Transcription Factor
0301 basic medicine Cardiomegaly Cell Line Muscle hypertrophy Mice 03 medical and health sciences Fibrosis Internal Medicine medicine Animals Myocytes Cardiac STAT3 Mice Knockout biology Interleukin-6 Chemistry Angiotensin II Atrial Remodeling Glycoprotein 130 medicine.disease Receptors Interleukin-6 Rats Cell biology Toll-Like Receptor 4 030104 developmental biology TLR4 biology.protein STAT protein Tyrosine kinase Signal Transduction |
| Zdroj: | Hypertension. 72:1301-1311 |
| ISSN: | 1524-4563 0194-911X |
| DOI: | 10.1161/hypertensionaha.118.11860 |
| Popis: | Evidence indicates that Ang II (angiotensin II) activates STAT3 (signal transducer and activator of transcription 3) in cardiomyocytes. However, the mechanisms underlying STAT3 activation and downstream responses are not fully known. In this study, we show that Ang II caused biphasic STAT3 activation in cardiomyocytes. A rapid and early activation was mediated by direct association between TLR4 (toll-like receptor-4) and STAT3. This early activation increased IL-6 (interleukin-6) production, which in turn, induced the second STAT3 activation through the IL-6/gp130 (glycoprotein 130)/JAK2 (Janus-family tyrosine kinases 2) pathway, resulting in unregulated expression of genes for cardiac remodeling. Moreover, STAT3 inhibition or TLR4 knockout in mice protected against Ang II–induced hypertrophy, fibrosis, and cardiac functional deficits. Thus, Ang II–induced STAT3 activation in cardiomyocytes was biphasic, providing a sequential induction of IL-6 and myocardial remodeling genes, respectively. This work supports a novel mechanism on STAT3 activation in Ang II–induced cardiac dysfunction and remodeling. |
| Databáze: | OpenAIRE |
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