Abstract
Galectin-1 protein (GAL-1) has important anti-inflammatory properties, but related pharmacologic approaches to effectively treat or prevent renal ischaemia and reperfusion injury are highly limited. Here, we investigated the effect of GAL-1 in a renal ischaemia-reperfusion injury rat model and an in vitro hypoxia-reoxygenation model with a proximal renal tubular epithelial cell line. In vivo, pretreatment with GAL-1 attenuated the renal parameters changed by ischaemia-reperfusion/hypoxia-reoxygenation, with recovery of renal function, protecting against influx of leukocytes, cell death and oxidative stress. Ischaemia-reperfusion/hypoxia-reoxygenation was also associated with increased renal endogenous expression of GAL-1 and intercellular adhesion molecule 1 (ICAM-1) plus augmented levels of proinflammatory cytokines IL-1β, TNF-α and MCP-1 and decreased anti-inflammatory IL-10 in urine, all of which were abrogated by GAL-1 treatment. In vitro studies demonstrated renal tubular epithelial cells as an important source of GAL-1 during hypoxia-reoxygenation and confirmed the protective effects of exogenous GAL-1 through downregulation of proinflammatory cytokine release by proximal renal tubular epithelial cells. Collectively, our findings confirm the important anti-inflammatory role of GAL-1 in kidney ischaemia and reperfusion injury and indicate its promising use as a therapeutic approach.
Highlights
Ischaemia-reperfusion (IR) occurs during procedures involved in the transplantation of organs and the damage caused by hypoxic IR in tubular cells represents the first event of acute renal failure[1,2]
DEXA and GAL-1-treated IR groups presented mild to moderate tissue injury of the juxtamedullary region
IR-induced renal injury results from a complex process involving the release of reactive oxygen species and proinflammatory mediators, the upregulation of adhesion molecules and leukocyte recruitment that culminates with rapid kidney dysfunction and high mortality rates[2,4]
Summary
Ischaemia-reperfusion (IR) occurs during procedures involved in the transplantation of organs and the damage caused by hypoxic IR in tubular cells represents the first event of acute renal failure[1,2]. GAL-1 is a 14.5 kDa protein that modulates cellular signalling, proliferation and survival and plays critical roles in the control of acute and chronic inflammation and neovascularization[6,7,8]. This lectin alters the secretion of cytokines, reducing levels of IL-2, IL-12, interferon gamma (IFN-γ) and tumour necrosis factor (TNF-α) and increasing IL-5 and IL-106,7,9,10. Given the acute renal failure is associated with increased risk of mortality and that the immune regulatory functions of GAL-1 in renal injury processes are poorly understood, we aimed to determine the mechanism of action of this lectin in an in vivo and an in vitro model of renal IR injury
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