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miR-181c, a potential mediator for acute kidney injury in a burn rat model with following sepsis

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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.

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References

  1. Snell JA, Loh NH, Mahambrey T, Shokrollahi K. Clinical review: the critical care management of the burn patient. Crit Care. 2013;17(5):241. https://doi.org/10.1186/cc12706.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Jeschke MG, van Baar ME, Choudhry MA, Chung KK, Gibran NS, Logsetty S. Burn injury. Nat Rev Dis Primers. 2020;6(1):11. https://doi.org/10.1038/s41572-020-0145-5.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Cecconi M, Evans L, Levy M, Rhodes A. Sepsis and septic shock. Lancet. 2018;392(10141):75–87. https://doi.org/10.1016/S0140-6736(18)30696-2.

    Article  PubMed  Google Scholar 

  4. Rech MA, Mosier MJ, McConkey K, Zelisko S, Netzer G, Kovacs EJ, et al. Outcomes in burn-injured patients who develop sepsis. J Burn Care Res. 2019;40(3):269–73. https://doi.org/10.1093/jbcr/irz017.

    Article  PubMed  PubMed Central  Google Scholar 

  5. AbuBakr HO, Aljuaydi SH, Abou-Zeid SM, El-Bahrawy A. Burn-induced multiple organ injury and protective effect of lutein in rats. Inflammation. 2018;41(3):760–72. https://doi.org/10.1007/s10753-018-0730-x.

    Article  CAS  PubMed  Google Scholar 

  6. Yu YH, Gaine GK, Zhou LY, Zhang JJ, Wang J, Sun BG. The classical and potential novel healthy functions of rice bran protein and its hydrolysates. Crit Rev Food Sci. 2021. https://doi.org/10.1080/10408398.2021.1929057.

    Article  Google Scholar 

  7. Folkestad T, Brurberg KG, Nordhuus KM, Tveiten CK, Guttormsen AB, Os I, et al. Acute kidney injury in burn patients admitted to the intensive care unit: a systematic review and meta-analysis. Crit Care. 2020;24(1):2. https://doi.org/10.1186/s13054-019-2710-4.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Rakkolainen I, Lindbohm JV, Vuola J. Factors associated with acute kidney injury in the Helsinki Burn Centre in 2006–2015. Scand J Trauma Resusc Emerg Med. 2018;26(1):105. https://doi.org/10.1186/s13049-018-0573-3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Emami A, Javanmardi F, Rajaee M, Pirbonyeh N, Keshavarzi A, Fotouhi M, et al. Predictive biomarkers for acute kidney injury in burn patients. J Burn Care Res. 2019;40(5):601–5. https://doi.org/10.1093/jbcr/irz065.

    Article  PubMed  Google Scholar 

  10. Assadi F, Sharbaf FG. Urine KIM-1 as a potential biomarker of acute renal injury after circulatory collapse in children. Pediatr Emerg Care. 2019;35(2):104–7. https://doi.org/10.1097/PEC.0000000000000886.

    Article  PubMed  Google Scholar 

  11. Munoz B, Suarez-Sanchez R, Hernandez-Hernandez O, Franco-Cendejas R, Cortes H, Magana JJ. From traditional biochemical signals to molecular markers for detection of sepsis after burn injuries. Burns. 2019;45(1):16–31. https://doi.org/10.1016/j.burns.2018.04.016.

    Article  PubMed  Google Scholar 

  12. Zou YF, Zhang W. Role of microRNA in the detection, progression, and intervention of acute kidney injury. Exp Biol Med (Maywood). 2018;243(2):129–36. https://doi.org/10.1177/1535370217749472.

    Article  CAS  PubMed  Google Scholar 

  13. Yu YH, Zhang JJ, Wang J, Sun BG. MicroRNAs: the novel mediators for nutrient-modulating biological functions. Trends Food Sci Tech. 2021;114:167–75. https://doi.org/10.1016/j.tifs.2021.05.028.

    Article  CAS  Google Scholar 

  14. Liang P, Lv C, Jiang B, Long X, Zhang P, Zhang M, et al. MicroRNA profiling in denatured dermis of deep burn patients. Burns. 2012;38(4):534–40. https://doi.org/10.1016/j.burns.2011.10.014.

    Article  PubMed  Google Scholar 

  15. Zhang Y, Yin B, Shu B, Liu Z, Ding H, Jia C. Differential expression of microRNA let-7b-5p regulates burn-induced hyperglycemia. Oncotarget. 2017;8(42):72886–92. https://doi.org/10.18632/oncotarget.20543.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Yu Y, Chai J, Zhang H, Chu W, Liu L, Ma L, et al. miR-194 Promotes burn-induced hyperglycemia via attenuating IGF-IR expression. Shock. 2014;42(6):578–84. https://doi.org/10.1097/SHK.0000000000000258.

    Article  CAS  PubMed  Google Scholar 

  17. Yu Y, Li X, Liu L, Chai J, Haijun Z, Chu W, et al. miR-628 promotes burn-induced skeletal muscle atrophy via targeting IRS1. Int J Biol Sci. 2016;12(10):1213–24. https://doi.org/10.7150/ijbs.15496.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Yu Y, Yang L, Han S, Wu Y, Liu L, Chang Y, et al. MIR-190B alleviates cell autophagy and burn-induced skeletal muscle wasting via modulating PHLPP1/Akt/FoxO3A signaling pathway. Shock. 2019;52(5):513–21. https://doi.org/10.1097/SHK.0000000000001284.

    Article  CAS  PubMed  Google Scholar 

  19. Li X, Liu L, Yang J, Yu Y, Chai J, Wang L, et al. Exosome derived from human umbilical cord mesenchymal stem cell mediates MiR-181c attenuating burn-induced excessive inflammation. EBioMedicine. 2016;8:72–82. https://doi.org/10.1016/j.ebiom.2016.04.030.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Yu Y, Chai J. The function of miRNAs and their potential as therapeutic targets in burn-induced insulin resistance (review). Int J Mol Med. 2015;35(2):305–10. https://doi.org/10.3892/ijmm.2014.2023.

    Article  CAS  PubMed  Google Scholar 

  21. Yu Y, Chu W, Chai J, Li X, Liu L, Ma L. Critical role of miRNAs in mediating skeletal muscle atrophy (Review). Mol Med Rep. 2016;13(2):1470–4. https://doi.org/10.3892/mmr.2015.4748.

    Article  CAS  PubMed  Google Scholar 

  22. Ju M, Liu B, He H, Gu Z, Liu Y, Su Y, et al. MicroRNA-27a alleviates LPS-induced acute lung injury in mice via inhibiting inflammation and apoptosis through modulating TLR4/MyD88/NF-kappaB pathway. Cell Cycle. 2018;17(16):2001–18. https://doi.org/10.1080/15384101.2018.1509635.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Zhang W, Shu L. Upregulation of miR-21 by ghrelin ameliorates ischemia/reperfusion-induced acute kidney injury by inhibiting inflammation and cell apoptosis. DNA Cell Biol. 2016;35(8):417–25. https://doi.org/10.1089/dna.2016.3231.

    Article  CAS  PubMed  Google Scholar 

  24. Zhao F, Yu Y, Liu W, Zhang J, Liu X, Liu L, et al. Small molecular weight soybean protein-derived peptides nutriment attenuates rat burn injury-induced muscle atrophy by modulation of ubiquitin-proteasome system and autophagy signaling pathway. J Agric Food Chem. 2018;66(11):2724–34. https://doi.org/10.1021/acs.jafc.7b05387.

    Article  CAS  PubMed  Google Scholar 

  25. Napier BA, Andres-Terre M, Massis LM, Hryckowian AJ, Higginbottom SK, Cumnock K, et al. Western diet regulates immune status and the response to LPS-driven sepsis independent of diet-associated microbiome. Proc Natl Acad Sci USA. 2019;116(9):3688–94. https://doi.org/10.1073/pnas.1814273116.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Nair AR, Masson GS, Ebenezer PJ, Del Piero F, Francis J. Role of TLR4 in lipopolysaccharide-induced acute kidney injury: protection by blueberry. Free Radical Biol Med. 2014;71:16–25. https://doi.org/10.1016/j.freeradbiomed.2014.03.012.

    Article  CAS  Google Scholar 

  27. Ronco C, Bellomo R, Kellum JA. Acute kidney injury. Lancet. 2019;394(10212):1949–64. https://doi.org/10.1016/S0140-6736(19)32563-2.

    Article  CAS  PubMed  Google Scholar 

  28. Harrois A, Libert N, Duranteau J. Acute kidney injury in trauma patients. Curr Opin Crit Care. 2017;23(6):447–56. https://doi.org/10.1097/MCC.0000000000000463.

    Article  PubMed  Google Scholar 

  29. Rabb H, Griffin MD, McKay DB, Swaminathan S, Pickkers P, Rosner MH, et al. Inflammation in AKI: current understanding, key questions, and knowledge gaps. J Am Soc Nephrol. 2016;27(2):371–9. https://doi.org/10.1681/ASN.2015030261.

    Article  CAS  PubMed  Google Scholar 

  30. Ren Q, Guo F, Tao S, Huang R, Ma L, Fu P. Flavonoid fisetin alleviates kidney inflammation and apoptosis via inhibiting Src-mediated NF-kappaB p65 and MAPK signaling pathways in septic AKI mice. Biomed Pharmacother. 2020;122:109772. https://doi.org/10.1016/j.biopha.2019.109772.

    Article  CAS  PubMed  Google Scholar 

  31. Inaba A, Tuong ZK, Riding AM, Mathews RJ, Martin JL, Saeb-Parsy K, et al. B lymphocyte-derived CCL7 augments neutrophil and monocyte recruitment. Exacerbating Acute Kidney Injury J Immunol. 2020;205(5):1376–84. https://doi.org/10.4049/jimmunol.2000454.

    Article  CAS  PubMed  Google Scholar 

  32. Rabadi MM, Han SJ, Kim M, D’Agati V, Lee HT. Peptidyl arginine deiminase-4 exacerbates ischemic AKI by finding NEMO. Am J Physiol Renal Physiol. 2019;316(6):F1180–90. https://doi.org/10.1152/ajprenal.00089.2019.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Martin-Sanchez D, Ruiz-Andres O, Poveda J, Carrasco S, Cannata-Ortiz P, Sanchez-Nino MD, et al. Ferroptosis, but not necroptosis, is important in nephrotoxic folic acid-induced AKI. J Am Soc Nephrol. 2017;28(1):218–29. https://doi.org/10.1681/ASN.2015121376.

    Article  CAS  PubMed  Google Scholar 

  34. Winchurch RA, Thupari JN, Munster AM. Endotoxemia in burn patients: levels of circulating endotoxins are related to burn size. Surgery. 1987;102(5):808–12.

    CAS  PubMed  Google Scholar 

  35. O’Neill LA, Bowie AG. The family of five: TIR-domain-containing adaptors in Toll-like receptor signalling. Nat Rev Immunol. 2007;7(5):353–64. https://doi.org/10.1038/nri2079.

    Article  CAS  PubMed  Google Scholar 

  36. Suzuki N, Suzuki S, Yeh WC. IRAK-4 as the central TIR signaling mediator in innate immunity. Trends Immunol. 2002;23(10):503–6. https://doi.org/10.1016/s1471-4906(02)02298-6.

    Article  CAS  PubMed  Google Scholar 

  37. Yu Y, Zhou L, Li X, Liu J, Li H, Gong L, et al. The progress of nomenclature, structure, metabolism, and bioactivities of oat novel phytochemical: avenanthramides. J Agric Food Chem. 2022;70(2):446–57. https://doi.org/10.1021/acs.jafc.1c05704.

    Article  CAS  PubMed  Google Scholar 

  38. Gorina R, Font-Nieves M, Marquez-Kisinousky L, Santalucia T, Planas AM. Astrocyte TLR4 activation induces a proinflammatory environment through the interplay between MyD88-dependent NFkappaB signaling, MAPK, and Jak1/Stat1 pathways. Glia. 2011;59(2):242–55. https://doi.org/10.1002/glia.21094.

    Article  PubMed  Google Scholar 

  39. Yu Y, Zhang D, Huang H, Li J, Zhang M, Wan Y, et al. NF-kappaB1 p50 promotes p53 protein translation through miR-190 downregulation of PHLPP1. Oncogene. 2014;33(8):996–1005. https://doi.org/10.1038/onc.2013.8.

    Article  CAS  PubMed  Google Scholar 

  40. Gaede L, Liebetrau C, Blumenstein J, Troidl C, Dorr O, Kim WK, et al. Plasma microRNA-21 for the early prediction of acute kidney injury in patients undergoing major cardiac surgery. Nephrol Dial Transplant. 2016;31(5):760–6. https://doi.org/10.1093/ndt/gfw007.

    Article  CAS  PubMed  Google Scholar 

  41. Li YF, Jing Y, Hao J, Frankfort NC, Zhou X, Shen B, et al. MicroRNA-21 in the pathogenesis of acute kidney injury. Protein Cell. 2013;4(11):813–9. https://doi.org/10.1007/s13238-013-3085-y.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Zhang L, He S, Wang Y, Zhu X, Shao W, Xu Q, et al. miRNA-20a suppressed lipopolysaccharide-induced HK-2 cells injury via NFkappaB and ERK1/2 signaling by targeting CXCL12. Mol Immunol. 2020;118:117–23. https://doi.org/10.1016/j.molimm.2019.12.009.

    Article  CAS  PubMed  Google Scholar 

  43. Li X, Liao J, Su X, Li W, Bi Z, Wang J, et al. Human urine-derived stem cells protect against renal ischemia/reperfusion injury in a rat model via exosomal miR-146a-5p which targets IRAK1. Theranostics. 2020;10(21):9561–78. https://doi.org/10.7150/thno.42153.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Lech M, Grobmayr R, Ryu M, Lorenz G, Hartter I, Mulay SR, et al. Macrophage phenotype controls long-term AKI outcomes–kidney regeneration versus atrophy. J Am Soc Nephrol. 2014;25(2):292–304. https://doi.org/10.1681/ASN.2013020152.

    Article  CAS  PubMed  Google Scholar 

  45. Lv LL, Feng Y, Wu M, Wang B, Li ZL, Zhong X, et al. Exosomal miRNA-19b-3p of tubular epithelial cells promotes M1 macrophage activation in kidney injury. Cell Death Differ. 2020;27(1):210–26. https://doi.org/10.1038/s41418-019-0349-y.

    Article  CAS  PubMed  Google Scholar 

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Funding

This work was supported by the Beijing Nova Program (Z181100006218043), the National Natural Science foundation of China (81772067) and the Beijing Natural Science Foundation (7172210).

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Authors and Affiliations

  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

    Yonghui Yu, Jingjie Zhang & Jing Wang

  2. The Fourth Medical Center of PLA General Hospital, 51 Fucheng Road, Haidian District, Beijing, 100048, China

    Xiao Li, Shaofang Han & Jiake Chai

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  1. Yonghui Yu
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  2. Xiao Li
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  3. Shaofang Han
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  4. Jingjie Zhang
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Contributions

YHY, XL, JJZ and JKC conceived the study; YHY and XL performed the experiments; YHY, XL, SFH, JW, JJZ and JKC analyzed the data; YHY and JJZ wrote the manuscript; JJZ and JKC approved the manuscript.

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Correspondence to Jingjie Zhang or Jiake Chai.

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The authors declare no conflicts of interest.

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All procedures for animal model had been approved, and the approval number was PONY-2020-FL-43.

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Yu, Y., Li, X., Han, S. et al. miR-181c, a potential mediator for acute kidney injury in a burn rat model with following sepsis. Eur J Trauma Emerg Surg 49, 1035–1045 (2023). https://doi.org/10.1007/s00068-022-02124-5

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