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TGF-β/Smad3 pathway enhances the cardio-protection of S1R/SIPR1 in in vitro ischemia-reperfusion myocardial cell model
Ischemia-reperfusion (IR) injury is usually associated with a high risk of cardiomyocyte death in patients with acute myocardial infarction. Sphingosine 1-phosphate (S1P) and transforming growth factor (TGF)-β are thought to be involved in the protection of cardiomyocyte and heart function following...
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Published in: | Experimental and therapeutic medicine 2018-07, Vol.16 (1), p.178-184 |
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Main Authors: | , , , |
Format: | Article |
Language: | English |
Subjects: | |
Online Access: | Get full text |
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Summary: | Ischemia-reperfusion (IR) injury is usually associated with a high risk of cardiomyocyte death in patients with acute myocardial infarction. Sphingosine 1-phosphate (S1P) and transforming growth factor (TGF)-β are thought to be involved in the protection of cardiomyocyte and heart function following IR-induced injury. However, the possible association of S1P and S1P receptor 1 (S1PR1) with the TGF-β/Smad3 pathway as the potential protective mechanism has remained to be investigated. In the present study, an
ischemia/reperfusion injury model was established and evaluated by analysis of apoptosis, lactate dehydrogenase (LDH) release and caspase3 activity. The mRNA and protein levels of S1PR1, TGF-β and Smad3 after treatment with 1 µM S1P alone or combined with 0.4 µM W146 (a specific S1PR1 antagonist) were assessed. The mRNA expression of five S1PRs (S1PR1-5) and the protein levels of S1PR1 were also assayed following treatment with 1 ng/ml TGF-β for 0, 4 or 24 h. The mRNA expression of S1PR1 and the levels of S1P were further assessed following exposure to 10 µM SB4 (TGFβR1 inhibitor) plus 1 ng/ml TGF-β and 2 µM SIS3 (Smad3 inhibitor) plus 1 ng/ml TGF-β. The results indicated that apoptosis, LDH release and caspase3 activity were all increased in the established IR model. Exogenous S1P increased the mRNA and protein levels of S1PR1, TGF-β and Smad3, which was abolished by addition of W146. Extraneous TGF-β resulted in the stimulation of several S1PRs, most prominently of S1PR1, while supplementation with SB4 and SIS3 offset the stimulation by TGF-β. These results suggested that the TGF-β/Smad3 pathway was closely associated with S1P/S1PR1 in the protection of myocardial cells from IR injury. |
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ISSN: | 1792-0981 1792-1015 |
DOI: | 10.3892/etm.2018.6192 |