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miR-128-3p Inhibits NRP1 Expression and Promotes Inflammatory Response to Acute Kidney Injury in Sepsis

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Abstract

The aims of this study were to find a treatment for acute kidney injury in sepsis and study the role of miR-128-3p in this process. We generated a model of septic acute kidney injury through cecal ligation and puncture (CLP) induction and screened differentially expressed microRNAs through microarray. The mechanism used by miR-128-3p in inflammatory response to septic acute kidney injury was investigated using cell transfection assay, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), flow cytometry, enzyme-linked immunosorbent assay, western blot, and Dual-Luciferase Reporter Assay. miRNA microarray screening revealed that miR-128-3p was significantly upregulated in the kidneys of mice with CLP-induced septic acute kidney injury. The level of inflammatory factors TNF-α, IL-1 β, and IL-6 decreased. In contrast, cell viability increased and apoptosis decreased with the addition of miR-128-3p inhibitors in TCMK-1 cells treated with lipopolysaccharide (LPS). Using bioinformatics and luciferin reporter gene experiments, we found that NRP1 is a miR-128-3p target gene. Overexpression of NRP1 in LPS-treated TCMK-1 cells decreased the expression of TNF-α, IL-6, and IL-1β; increased cell viability; and decreased apoptosis. The survival period of mice pretreated with miR-128-3p inhibitors was prolonged, infiltration of inflammatory cells into kidney tissue decreased, permeability of kidneys enhanced, and expression of inflammatory factors and renal apoptosis decreased. miR-128-3p targets NRP1 for cell degradation, promotes inflammatory cell infiltration, increases expression of inflammatory factors, decreases renal cell viability, and increases apoptosis in LPS-induced septic acute renal injury.

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References

  1. Godin, M., P. Murray, and R.L. Mehta. 2015. Clinical approach to the patient with AKI and sepsis. Seminars in Nephrology 35 (1): 12–22.

    Article  Google Scholar 

  2. Bellomo, R., J.A. Kellum, C. Ronco, R. Wald, J. Martensson, M. Maiden, S.M. Bagshaw, N.J. Glassford, Y. Lankadeva, S.T. Vaara, and A. Schneider. 2017. Acute kidney injury in sepsis. Intensive Care Medicine 43 (6): 816–828.

    Article  CAS  Google Scholar 

  3. Hummeke-Oppers, F., P. Hemelaar, and P. Pickkers. 2019. Innovative drugs to target renal inflammation in sepsis: Alkaline phosphatase. Frontiers in Pharmacology 10: 919.

    Article  Google Scholar 

  4. Adams, B.D., C. Parsons, L. Walker, W.C. Zhang, and F.J. Slack. 2017. Targeting noncoding RNAs in disease. The Journal of Clinical Investigation 127 (3): 761–771.

    Article  Google Scholar 

  5. Andreucci, M., T. Faga, A. Pisani, M. Perticone, and A. Michael. 2017. The ischemic/nephrotoxic acute kidney injury and the use of renal biomarkers in clinical practice. European Journal of Internal Medicine 39: 1–8.

    Article  CAS  Google Scholar 

  6. Chen, Y., J. Qiu, B. Chen, Y. Lin, Y. Chen, G. Xie, J. Qiu, H. Tong, and D. Jiang. 2018. Long non-coding RNA NEAT1 plays an important role in sepsis-induced acute kidney injury by targeting miR-204 and modulating the NF-κB pathway. International Immunopharmacology 59: 252–260.

    Article  CAS  Google Scholar 

  7. Wang, S., et al. 2017. MiR-107 induces TNF-α secretion in endothelial cells causing tubular cell injury in patients with septic acute kidney injury. Biochemical and Biophysical Research Communications.

  8. Colbert, J.F., J.A. Ford, S.M. Haeger, Y. Yang, K.L. Dailey, K.C. Allison, V. Neudecker, C.M. Evans, V.L. Richardson, K.S. Brodsky, S. Faubel, H.K. Eltzschig, E.P. Schmidt, and A.A. Ginde. 2017. A model-specific role of microRNA-223 as a mediator of kidney injury during experimental sepsis. American Journal of Physiology. Renal Physiology 313 (2): F553–f559.

    Article  CAS  Google Scholar 

  9. Xia, Z., Meng F., Liu Y., Fang Y., Wu X., Zhang C., Liu D., Li G., Decreased miR-128 expression alleviated the progression of rheumatoid arthritis by up-regulating the expression of TNFAIP3. Bioscience Reports, 2018, 38.

  10. Wu, L., et al., MiR-128-3p mediates TNF-α-induced inflammatory responses by regulating Sirt1 expression in bone marrow mesenchymal stem cells. Biochemical and Biophysical Research Communications, 2019.

  11. Das, S., R. Periyasamy, and K.N. Pandey. 2012. Activation of IKK/NF-kappaB provokes renal inflammatory responses in guanylyl cyclase/natriuretic peptide receptor-A gene-knockout mice. Physiological Genomics 44 (7): 430–442.

    Article  CAS  Google Scholar 

  12. Ma, Y., Z. Zhang, R. Chen, R. Shi, P. Zeng, R. Chen, Y. Leng, and A.F. Chen. 2019. NRP1 regulates HMGB1 in vascular endothelial cells under high homocysteine condition. American Journal of Physiology. Heart and Circulatory Physiology 316: H1039–H1046.

    Article  CAS  Google Scholar 

  13. Ma, L., B. Zhai, H. Zhu, W. Li, W. Jiang, L. Lei, S. Zhang, H. Qiao, X. Jiang, and X. Sun. 2019. The miR-141/neuropilin-1 axis is associated with the clinicopathology and contributes to the growth and metastasis of pancreatic cancer. Cancer Cell International 19: 248.

    Article  Google Scholar 

  14. Hang, C., H.S. Yan, C. Gong, H. Gao, Q.H. Mao, and J.X. Zhu. 2019. MicroRNA-9 inhibits gastric cancer cell proliferation and migration by targeting neuropilin-1. Experimental and Therapeutic Medicine 18 (4): 2524–2530.

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Wei, Q.F., J.S. Yao, and Y.T. Yang. 2019. MicroRNA-1247 inhibits the viability and metastasis of osteosarcoma cells via targeting NRP1 and mediating Wnt/β-catenin pathway. European Review for Medical and Pharmacological Sciences 23 (17): 7266–7274.

    PubMed  Google Scholar 

  16. Wilson, R.L., V. Selvaraju, R. Lakshmanan, M. Thirunavukkarasu, J. Campbell, D.W. McFadden, and N. Maulik. 2017. Thioredoxin-1 attenuates sepsis-induced cardiomyopathy after cecal ligation and puncture in mice. The Journal of Surgical Research 220: 68–78.

    Article  CAS  Google Scholar 

  17. Singer, M., C.S. Deutschman, C.W. Seymour, M. Shankar-Hari, D. Annane, M. Bauer, R. Bellomo, G.R. Bernard, J.D. Chiche, C.M. Coopersmith, R.S. Hotchkiss, M.M. Levy, J.C. Marshall, G.S. Martin, S.M. Opal, G.D. Rubenfeld, T. van der Poll, J.L. Vincent, and D.C. Angus. 2016. The third international consensus definitions for sepsis and septic shock (Sepsis-3). JAMA 315 (8): 801–810.

    Article  CAS  Google Scholar 

  18. Coopersmith, C.M., D. de Backer, C.S. Deutschman, R. Ferrer, I. Lat, F.R. Machado, G.S. Martin, I. Martin-Loeches, M.E. Nunnally, M. Antonelli, L.E. Evans, J. Hellman, S. Jog, J. Kesecioglu, M.M. Levy, and A. Rhodes. 2018. Surviving sepsis campaign: Research priorities for sepsis and septic shock. Critical Care Medicine 46 (8): 1334–1356.

    Article  Google Scholar 

  19. Williams, J.M., G. Keijzers, S.P.J. Macdonald, A. Shetty, and J.F. Fraser. 2018. Review article: Sepsis in the emergency department - part 3: treatment. Emergency Medicine Australasia 30 (2): 144–151.

    Article  Google Scholar 

  20. Liu, J., et al., Selenomethionine alleviates LPS-induced chicken myocardial inflammation by regulating the miR-128-3p-p38 MAPK axis and oxidative stress. Metallomics, 2019.

  21. Xia, Z., et al., Decreased MiR-128-3p alleviates the progression of rheumatoid arthritis by up-regulating the expression of TNFAIP3. Bioscience Reports, 2018. 38(4).

  22. Wnuk, M., M.A. Anderegg, W.A. Graber, R. Buergy, D.G. Fuster, and V. Djonov. 2017. Neuropilin1 regulates glomerular function and basement membrane composition through pericytes in the mouse kidney. Kidney International 91 (4): 868–879.

    Article  CAS  Google Scholar 

  23. Nilsson, D., M. Heglind, Z. Arani, and S. Enerbäck. 2019. Foxc2 is essential for podocyte function. Physiological Reports 7 (9): e14083.

    Article  Google Scholar 

  24. Loeffler, I., C. Rüster, S. Franke, M. Liebisch, and G. Wolf. 2013. Erythropoietin ameliorates podocyte injury in advanced diabetic nephropathy in the db/db mouse. American Journal of Physiology. Renal Physiology 305 (6): F911–F918.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of ICU, ZiBo Central Hospital, 54 Gongqingtuan Road, Zhangdian District, Zibo, Shandong, China

    Lin Wang & Kai Wang

  2. Department of ICU, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, 16369 Jingshi Road, Lixia District, Jinan, Shandong, China

    Zhengyun Tian

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  1. Lin Wang
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Correspondence to Lin Wang.

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Wang, L., Wang, K. & Tian, Z. miR-128-3p Inhibits NRP1 Expression and Promotes Inflammatory Response to Acute Kidney Injury in Sepsis. Inflammation 43, 1772–1779 (2020). https://doi.org/10.1007/s10753-020-01251-8

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