Renal ischemia/reperfusion (I/R) injury continues to be a complicated situation in clinical practice. Genistein, the main isoflavone found in soy products, is known to possess a wide spectrum of biochemical and pharmacological activities. However, the protective effect of genistein on renal I/R injury has not been well investigated. In the current study, we explore whether genistein exhibits its renal-protective effects through SIRT1 (Sirtuin 1) in I/R-induced mice model. We found the treatment of genistein significantly reduced renal I/R-induced cell death, simultaneously stimulating renal cell proliferation. Meanwhile, SIRT1 expression was up-regulated following the administration of genistein in renal region. Furthermore, pharmacological inhibition or shRNA-mediated depletion of SIRT1 significantly reversed the protective effect of genistein on renal dysfunction, cellular damage, apoptosis, and proliferation following I/R injury, suggesting an indispensible role of the increased SIRT1 expression and activity in this process. Meanwhile, the reduced p53 and p21 expression and increased PCNA (Proliferating Cell Nuclear Antigen) expression were blocked after the depletion of SIRT1 compared with the genistein treatment group in the renal I/R process. Hence, our results provided further experimental basis for the potential use of genistein for the treatment of kidney disease with deficiency of SIRT1 activity.

Interleukin (IL)-33, is a novel member of the IL-1 superfamily, and act as a dual-function molecule as a nuclear factor and cytokine. The expression of IL-33 can be detected in several tissues and cells in humans and in mice. In addition to the conventional secretion approach for cytokines, full-length IL-33 can also be released into the extracellular space following cell damage or mechanical injury. IL-33 mediates its biological effects by interacting with the receptors, suppression of tumorigenicity 2 (ST2) and IL-1 receptor accessory protein, activating intracellular molecules in the nuclear factor-κB and mitogen-activated protein kinase signaling pathways, which drive the production of type 2 cytokines, including IL-4, IL-5 and IL-3, from polarized T helper 2 cells. Increasing evidence indicates that IL-33 is important in chronic kidney disease, and may be involved in the progression of renal fibrosis associated with systemic lupus erythematosus and renal graft damage. In addition, IL-33 contributes to acute kidney injury. In the present review, the biology of IL-33, and the association of IL-33 with kidney diseases are discussed.

High mobility group box 1 (HMGB1), a non-histone DNA-binding protein, regulates nucleosome function and transcription in the nuclei of all metazoans and plants. However, extracellular HMGB1, which is actively or passively released under different conditions, can act as a key inflammatory mediator through MyD88/mitogen-activated protein kinase signaling by binding to its receptors including the receptor for advanced glycation end products or Toll-like receptors. A growing body of evidence indicates that HMGB1 plays an important role in kidney diseases, such as glomerulonephritis, lupus nephritis, antineutrophilic cytoplasmatic antibody-associated vaculitis, diabetic nephropathy, renal allograft rejection and acute kidney injury. In this review, we focus on the biology of HMGB1 and the association of HMGB1 with kidney diseases.