Role of Nrf2 in Lipopolysaccharide-Induced Acute Kidney Injury: Protection by Human Umbilical Cord Blood Mononuclear Cells

Abstract

Background. Acute kidney injury (AKI) is one of the common complications of sepsis. Heretofore, there is no effective treatment for septic AKI. Recent studies have revealed that besides treating hematological malignancies, human umbilical cord blood mononuclear cells (hUCBMNCs) show good therapeutic effects on other diseases. But whether hUCBMNCs can protect against septic AKI and its underlying mechanism are unknown. Methods. The rat model of lipopolysaccharide- (LPS-) induced AKI was developed, and the injection of hUCBMNCs was executed to prevent and treat AKI. ML385, a specific nuclear factor E2-related factor 2 (Nrf2) inhibitor, was used to silence Nrf2. The cell experiments were conducted to elaborate the protective mechanism of Nrf2 pathway. Results. An effective model of LPS-induced AKI was established. Compared to the rats only with LPS injection, the levels of inflammation, reactive oxygen species (ROS), and apoptosis in renal tissues after hUCBMNC injection were markedly attenuated. Pathological examination also indicated significant remission of renal tissue injury in the LPS+MNCs group, compared to rats in the LPS group. Transmission electron microscopy (TEM) showed that the damage of the mitochondria in the LPS+MNCs group was lighter than that in the LPS group. Noteworthily, the renal Nrf2/HO-1 pathway was activated and autophagy was enhanced after hUCBMNC injection. ML385 could partly reverse the renoprotective effect of hUCBMNCs, which could demonstrate that Nrf2 participated in the protection of hUCBMNCs. Cell experiments showed that increasing the expression level of Nrf2 could alleviate LPS-induced cell injury by increasing the autophagy level and decreasing the injury of the mitochondria in HK-2 cells. Conclusion. All results suggest that hUCBMNCs can protect against LPS-induced AKI via the Nrf2 pathway. Activating Nrf2 can upregulate autophagy to protect LPS-induced cell injury.

Honokiol alleviates LPS-induced acute lung injury by inhibiting NLRP3 inflammasome-mediated pyroptosis via Nrf2 activation in vitro and in vivo

“…ML385 + HKL group was treated with ML385 (30 mg/kg, i.p. )[ 21 ] before LPS administration followed by HKL (2.5 mg/kg). After LPS intervention for 24 h, the rats were euthanized by injecting 100 mg/kg sodium pentobarbital intraperitoneally.…”

Downregulation of miR‐29b‐3p aggravates podocyte injury by targeting HDAC4 in LPS‐induced acute kidney injury

“…Sepsis is a severe organ dysfunction disease triggered by a dysregulated host response to infection. 1,2 The kidney is the most vulnerable organ after sepsis with high mortality. 1,6 Over 50% of patients with sepsis are accompanied by AKI.…”

“…Sepsis is an organ dysfunction disease triggered by the dysregulated host response to bacterial, viral, or fungal infections. 1,2 At present, sepsis is considered as the major cause of death in intensive care units (ICU). Sepsis is characterized by the excessive production of various inflammatory mediators, resulting in extensive cell and tissue damage.…”

“…2,5 Besides, the mortality of sepsis patients with AKI is higher than that of patients with AKI alone. 1,6 Therefore, it is a severe threat to public health. Thus, it is essential to investigate the sepsis-induced AKI mechanism and search for practical AKI treatment strategies after sepsis.…”

Honokiol alleviates LPS-induced acute lung injury by inhibiting NLRP3 inflammasome-mediated pyroptosis via Nrf2 activation in vitro and in vivo

“…ML385+HKL group was treated with ML385 (30 mg/kg, i.p.) [20]before LPS administration followed by HKL (2.5 mg/kg). After LPS intervention for 24 h, the rats were euthanized by injecting 100 mg/kg sodium pentobarbital intraperitoneally.…”