VASPIN reduces inflammation and endoplasmic reticulum stress of renal tubular epithelial cells by inhibiting HMGB1 and relieves renal ischemia-reperfusion injury

G.-Z. Zhang, K. Zhang, S.-Q. Yang, Z. Zhang, S. Chen, B.-J. Hou, J.-Y. Yuan

Department of Intensive Care Unit, Shanxian Central Hospital, Heze, China. tokitep@126.com

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• Nephrology

OBJECTIVE: Renal ischemia-reperfusion injury (IRI) is a clinically common issue and the resulting acute kidney injury (AKI) seriously threatens the patient’s life. Therefore, prevention and treatment of renal IRI are the key to alleviating AKI in such patients. The purpose of this study was to explore the effects of VASPIN on mouse renal IRI and human renal proximal tubular epithelial cells (HK-2 cells) to provide a new direction for the treatment of clinical renal IRI.

MATERIALS AND METHODS: C57/BL6 mice were used to construct a renal IRI model and recombinant mouse VASPIN was subcutaneously injected to determine whether VASPIN can alleviate renal IRI in mice by histological examination and detection of mouse urine and serum related indicators. In addition, HK-2 cells were cultured and an IRI model was constructed at the cellular level by hypoxia reoxygenation to examine the effect and mechanism of VASPIN on endoplasmic reticulum stress (ERS) in HK-2 cells.

RESULTS: Results revealed that in VASPIN-treated mice, edema of renal tubular epithelial cells was significantly improved and renal injury markers netrin-1 and L-FAPB were decreased in urine. In addition, VASPIN also reduced the expression of inflammatory factors in mouse serum and the level of oxidative stress in kidney tissue. The expression of ERS-related molecules (GRP78, ATF6, caspase12, and CHOP) in HK-2 cells treated with VASPIN was significantly reduced and VASPIN decreased the expression of the pro-inflammatory factor HMGB1. Moreover, VASPIN promoted the activity of the Nrf2/ARE/HO-1 signaling pathway and inhibited the NF-кB signaling pathway by inhibiting HMGB1.

CONCLUSIONS: VASPIN reduces inflammation and ERS levels in kidney tissue and attenuates renal IRI by activating the Nrf2/ARE/HO-1 signaling pathway and inhibiting the NF-кB signaling pathway via inhibition of HMGB1.

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