Key result
Targeted T-cell S1P receptor 1 deletion improves cardiac function and alleviates fibrosis in diabetic mice.
Why the study?
Does targeted deletion of T-cell S1P receptor 1 ameliorate cardiac fibrosis in streptozotocin-induced diabetic mice?
Does targeted deletion of T-cell S1P receptor 1 ameliorate cardiac fibrosis in streptozotocin-induced diabetic mice?
T-cell S1P1 signaling activation plays a dual role, exerting antifibrotic effects in normoglycemia but exacerbating cardiac fibrosis under hyperglycemia.
Hypothesis-generating for T-cell S1P1 in diabetic fibrosis; prospective human studies required before clinical consideration.
Infiltration of T cells is associated with patients who have diabetes at an increased risk of heart attack. T‐cell sphingosine 1‐phosphate receptor 1 (S1P 1 )‐mediated signaling directs T‐lymphocyte trafficking. Effects of T‐cell S1P 1 activation on cardiac fibrosis in a murine diabetic model remain to be explored. For this purpose, conditional T‐cell S1P 1 knockout (TS1P 1 KO) mice generated by crossing S1pr 1 loxP/loxP mice with Lck‐Cre mice were used in a model of streptozotocin‐induced diabetic cardiomyopathy. The TS1P 1 KO mice exhibited sustained deficiency of both CD4 + and CD8 + T cells in the blood. The TS1P 1 KO vehicle control mouse hearts featured an altered phenotype characterized by increased myocardial fibrosis and reduced cardiac contractility under normal levels of glucose. Compared with littermate diabetic mice, TS1P 1 KO diabetic mice had improved cardiac function and alleviated cardiac fibrosis detected after 11 wk of diabetic induction. Our results indicate that T‐cell S1P 1 signaling activation plays a dual role in the pathogenesis of cardiac fibrosis with respect to the levels of glucose: T‐cell S1P 1 activation exerts antifibrotic effects in normoglycemia but exacerbates fibrosis under hyperglycemia.—Abdullah, C. S., Jin, Z.‐Q. Targeted deletion of T‐cell S1P receptor 1 ameliorates cardiac fibrosis in streptozotocin‐induced diabetic mice. FASEB J. 32, 5426–5435 (2018). www.fasebj.org
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Chowdhury S. Abdullah (2018) studied Streptozotocin-induced diabetic cardiomyopathy. Targeted deletion of T-cell S1P receptor 1 (TS1P1KO) vs. Littermate diabetic mice / vehicle control mice was evaluated on Cardiac function and cardiac fibrosis. Targeted deletion of T-cell S1P receptor 1 improved cardiac function and alleviated cardiac fibrosis after 11 weeks of streptozotocin-induced diabetes in mice.
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