Yonghui Yu1, Xiao Li2, Shaofang Han2, Jingjie Zhang3, Jing Wang1, Jiake Chai4. 1. China-Canada Joint Lab of Food Nutrition and Health (Beijing), Key Laboratory of Special Food Supervision Technology for State Market Regulation, Beijing Advanced Innovation Center for Food Nutrition and Human Health, Beijing Technology and Business University, 11 Fucheng Road, Haidian District, Beijing, 100048, China. 2. The Fourth Medical Center of PLA General Hospital, 51 Fucheng Road, Haidian District, Beijing, 100048, China. 3. China-Canada Joint Lab of Food Nutrition and Health (Beijing), Key Laboratory of Special Food Supervision Technology for State Market Regulation, Beijing Advanced Innovation Center for Food Nutrition and Human Health, Beijing Technology and Business University, 11 Fucheng Road, Haidian District, Beijing, 100048, China. jingjiezhang@163.com. 4. The Fourth Medical Center of PLA General Hospital, 51 Fucheng Road, Haidian District, Beijing, 100048, China. cjk304@126.com.
Abstract
BACKGROUND: The miRNA profile is changed after burn or sepsis and is involved in regulating inflammatory reactions. However, the function and molecular mechanism of miRNAs in regulating burn sepsis-induced acute kidney injury (AKI) are still unclear. METHODS: In this study, animal and cell sepsis models were established after burned rats were injected with lipopolysaccharide (LPS) or NRK-52E cells treated with LPS, respectively. Cytokine expression, inflammatory cell infiltration, serum creatinine (Scr) and kidney injury molecule-1 (KIM-1) levels were analysed after the indicated treatments. RESULTS: Burn sepsis increased the expression of inflammatory factors (TNF-α and IL-1β) and chemokines (MIP-1α, MIP-2 and MCP-1). Moreover, burn sepsis promoted macrophage and neutrophil infiltration into the kidney and upregulated the levels of Scr and KIM-1 in the kidney and urine. Ectopic expression of miR-181c significantly reduced LPS-induced TLR4 protein expression, suppressed KIM-1 mRNA levels and subsequently inhibited the activation of inflammatory genes (TNF-α and IL-1β) and chemokine genes (MIP-1α, MIP-2 and MCP-1). CONCLUSIONS: Our results demonstrated that miR-181c could suppress TLR4 expression, reduce inflammatory factor and chemokine secretion, mitigate inflammatory cell infiltration into the kidney and downregulate KIM-1 expression, which might ultimately attenuate burn sepsis-induced AKI.
BACKGROUND: The miRNA profile is changed after burn or sepsis and is involved in regulating inflammatory reactions. However, the function and molecular mechanism of miRNAs in regulating burn sepsis-induced acute kidney injury (AKI) are still unclear. METHODS: In this study, animal and cell sepsis models were established after burned rats were injected with lipopolysaccharide (LPS) or NRK-52E cells treated with LPS, respectively. Cytokine expression, inflammatory cell infiltration, serum creatinine (Scr) and kidney injury molecule-1 (KIM-1) levels were analysed after the indicated treatments. RESULTS: Burn sepsis increased the expression of inflammatory factors (TNF-α and IL-1β) and chemokines (MIP-1α, MIP-2 and MCP-1). Moreover, burn sepsis promoted macrophage and neutrophil infiltration into the kidney and upregulated the levels of Scr and KIM-1 in the kidney and urine. Ectopic expression of miR-181c significantly reduced LPS-induced TLR4 protein expression, suppressed KIM-1 mRNA levels and subsequently inhibited the activation of inflammatory genes (TNF-α and IL-1β) and chemokine genes (MIP-1α, MIP-2 and MCP-1). CONCLUSIONS: Our results demonstrated that miR-181c could suppress TLR4 expression, reduce inflammatory factor and chemokine secretion, mitigate inflammatory cell infiltration into the kidney and downregulate KIM-1 expression, which might ultimately attenuate burn sepsis-induced AKI.
Authors: Megan A Rech; Michael J Mosier; Kevin McConkey; Susan Zelisko; Giora Netzer; Elizabeth J Kovacs; Majid Afshar Journal: J Burn Care Res Date: 2019-04-26 Impact factor: 1.845
Authors: Marc G Jeschke; Margriet E van Baar; Mashkoor A Choudhry; Kevin K Chung; Nicole S Gibran; Sarvesh Logsetty Journal: Nat Rev Dis Primers Date: 2020-02-13 Impact factor: 52.329