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IL-33 receptor ST2 deficiency attenuates renal ischaemia–reperfusion injury in euglycaemic, but not streptozotocin-induced hyperglycaemic mice

Abstract : AIM: Kidney hypoxia can predispose to the development of acute and chronic renal failure in diabetes. Ischaemia-reperfusion injury (IRI) causes inflammation, and diabetes is known to exacerbate this inflammatory response in the kidney, whereas alarmin IL-33 could act as an innate immune mediator during kidney IRI. Thus, the present study examined the impact of genetic IL-33 receptor ST2 deficiency (ST2-/-) on renal IRI in euglycaemic and hyperglycaemic mice. METHODS: Hyperglycaemia was induced with streptozotocin (STZ) in adult male C57BL/6JRj wild-type (WT) mice and ST2-/- mice. Unilateral renal IRI was achieved 3months after STZ treatment by left kidney nephrectomy (non-ischaemic control kidney) and clamping of the right renal artery for 32min in STZ- and vehicle-treated animals. At 24h after reperfusion, renal function and injury were determined by levels of plasma creatinine, blood urea nitrogen (BUN) and histological tubule scores. Also, in a complementary pilot clinical study, soluble ST2 concentrations were compared in diabetics and non-diabetics. RESULTS: Urinary albumin was significantly increased in STZ-induced hyperglycaemic mice, regardless of genotypic background. At 24h post-ischaemia, plasma creatinine, BUN and tubular injury were significantly reduced in ST2-/- mice compared with vehicle-treated WT mice, but this protective effect was lost in the STZ-induced hyperglycaemic ST2-/- animals. Plasma concentrations of soluble ST2 were significantly greater in type 2 diabetes patients vs non-diabetics. CONCLUSION: Our data suggest that the IL-33/ST2 pathway exerts differential effects depending on the glucose environment, opening-up new avenues for future research on alarmins and diabetes in ischaemia-related diseases.
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https://www.hal.inserm.fr/inserm-01617712
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Submitted on : Monday, October 16, 2017 - 11:36:23 PM
Last modification on : Tuesday, May 12, 2020 - 4:34:33 PM

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M. Sehnine, M. Ferhat, S. Sena, J.M. Gombert, J.M. Goujon, et al.. IL-33 receptor ST2 deficiency attenuates renal ischaemia–reperfusion injury in euglycaemic, but not streptozotocin-induced hyperglycaemic mice. Journal of Diabetes & Metabolism, OMICS International, 2018, 44 (1), pp.55-60. ⟨10.1016/j.diabet.2017.06.008⟩. ⟨inserm-01617712⟩

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