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MicroRNA let-7c Improves LPS-Induced Outcomes of Endometritis by Suppressing NF-κB Signaling

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Abstract

Endometritis is a common inflammatory disease which endangers human and animal reproductive health. MicroRNA (miRNA) let-7c plays an important role in the inflammatory process; however, the regulatory underlying mechanism of let-7c in endometritis is unclear. In this study, we confirmed that let-7c was significantly reduced in LPS-induced mouse endometritis model, and overexpression of let-7c was able to effectively reduce uterine tissue damage caused by lipopolysaccharide (LPS), and then, a LPS-induced bovine endometrial epithelial cell (BEND) line was used to mimic the inflammatory model in vitro. Our data showed that overexpression of let-7c significantly reduced the expression of pro-inflammatory cytokines in BEND cells induced by LPS. Meanwhile, immunofluorescence and western blotting results showed that let-7c significantly inhibited LPS-induced phosphorylation of NF-κB, thereby inhibiting downstream pro-inflammatory cytokine expression. Taken together, our results suggested that let-7c ameliorates LPS-induced endometritis by attenuating the expression of pro-inflammatory cytokines via inhibition of the activation of NF-κB.

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References

  1. Polisseni, F., E.A. Bambirra, and A.F. Camargos. 2003. Detection of chronic endometritis by diagnostic hysteroscopy in asymptomatic infertile patients. Gynecologic and Obstetric Investigation 55 (4): 205–210. https://doi.org/10.1159/000072075.

    Article  PubMed  Google Scholar 

  2. Gan, Zhao, Chao Yang, Jing Yang, Pei Liu, Kangfeng Jiang, Aftab Shaukat, Haichong Wu, and Ganzhen Deng. 2018. Placental exosome-mediated Bta-miR-499-Lin28B/let-7 axis regulates inflammatory bias during early pregnancy. Cell Death & Disease 9 (6): 704. https://doi.org/10.1038/s41419-018-0713-8.

    Article  Google Scholar 

  3. Zhao, H.X., J.L. Zhao, J.Z. Shen, H.L. Fan, H. Guan, X.P. An, and P.F. Li. 2014. Prevalence and molecular characterization of fluoroquinolone resistance in Escherichia coli isolates from dairy cattle with endometritis in China. Microbial Drug Resistance 20 (2): 162–169. https://doi.org/10.1089/mdr.2013.0073.

    Article  CAS  PubMed  Google Scholar 

  4. Sens, A., and W. Heuwieser. 2013. Presence of Escherichia coli, Trueperella pyogenes, alpha-hemolytic streptococci, and coagulase-negative staphylococci and prevalence of subclinical endometritis. Journal of Dairy Science 96 (10): 6347–6354. https://doi.org/10.3168/jds.2013-6646.

    Article  CAS  PubMed  Google Scholar 

  5. Didier, Heumann, and Thierry Roger. 2002. Initial responses to endotoxins and Gram-negative bacteria. Clinica Chimica Acta 323 (1–2): 59–72.

    Google Scholar 

  6. Kim, M.E., I. Jung, J.S. Lee, J.Y. Na, W.J. Kim, Y.O. Kim, Y.D. Park, and J.S. Lee. 2017. Pseudane-VII isolated from Pseudoalteromonas sp. M2 ameliorates LPS-induced inflammatory response in vitro and in vivo. Marine Drugs 15 (11): 336. https://doi.org/10.3390/md15110336.

    Article  CAS  PubMed Central  Google Scholar 

  7. Fu, K., X. Lv, W. Li, Y. Wang, H. Li, W. Tian, and R. Cao. 2015. Berberine hydrochloride attenuates lipopolysaccharide-induced endometritis in mice by suppressing activation of NF-κB signal pathway. International Immunopharmacology 24 (1): 128–132. https://doi.org/10.1016/j.intimp.2014.11.002.

    Article  CAS  PubMed  Google Scholar 

  8. Zhao, G., K. Jiang, Y. Yang, T. Zhang, H. Wu, A. Shaukat, C. Qiu, and G. Deng. 2018. The potential therapeutic role of miR-223 in bovine endometritis by targeting the NLRP3 inflammasome. Frontiers in Immunology 9: 1916. https://doi.org/10.3389/fimmu.2018.01916.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Chen, Y., Z. Wu, B. Yuan, Y. Dong, L. Zhang, and Z. Zeng. 2018. MicroRNA-146a-5p attenuates irradiation-induced and LPS-induced hepatic stellate cell activation and hepatocyte apoptosis through inhibition of TLR4 pathway. Cell Death & Disease 9 (2): 22. https://doi.org/10.1038/s41419-017-0038-z.

    Article  Google Scholar 

  10. Wu, Haichong, Zhao Gan, Kangfeng Jiang, Chengye Li, Changwei Qiu, and Ganzhen Deng. 2016. Engeletin alleviates lipopolysaccharide-induced endometritis in mice by inhibiting TLR4-mediated NF-κB activation. Journal of Agricultural and Food Chemistry 64 (31): 6171–6178. https://doi.org/10.1021/acs.jafc.6b02304.

    Article  CAS  PubMed  Google Scholar 

  11. Wang, Xiaoyu, Shuangshuang Chen, Jingshu Ni, Jian Cheng, Jia Jia, and Xuechu Zhen. 2018. miRNA-3473b contributes to neuroinflammation following cerebral ischemia. Cell Death & Disease 9 (1): 11. https://doi.org/10.1038/s41419-017-0014-7.

    Article  Google Scholar 

  12. Sami, Banerjee, Na Xie, Huachun Cui, Zheng Tan, Shanzhong Yang, Mert Icyuz, Edward Abraham, and Gang Liu. 2013. microRNA let-7c regulates macrophage polarization. Journal of Immunology 190 (12): 6542–6549. https://doi.org/10.4049/jimmunol.1202496.

    Article  CAS  Google Scholar 

  13. Zhang, W., H. Liu, W. Liu, Y. Liu, and J. Xu. 2015. Polycomb-mediated loss of microRNA let-7c determines inflammatory macrophage polarization via PAK1-dependent NF-kappaB pathway. Cell Death and Differentiation 22 (2): 287–297. https://doi.org/10.1038/cdd.2014.142.

    Article  CAS  PubMed  Google Scholar 

  14. Iliopoulos, Dimitrios, Heather A. Hirsch, and Kevin Struhl. 2009. An epigenetic switch involving NF-κB, Lin28, Let-7 MicroRNA, and IL6 links inflammation to cell transformation. Cell 139 (4): 693–706. https://doi.org/10.1016/j.cell.2009.10.014.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Lv, J., Y. Zeng, Y. Qian, J. Dong, Z. Zhang, and J. Zhang. 2018. MicroRNA let-7c-5p improves neurological outcomes in a murine model of traumatic brain injury by suppressing neuroinflammation and regulating microglial activation. Brain Research 1685: 91–104. https://doi.org/10.1016/j.brainres.2018.01.032.

    Article  CAS  PubMed  Google Scholar 

  16. Zhao, G., T. Zhang, X. Ma, K. Jiang, H. Wu, C. Qiu, M. Guo, and G. Deng. 2017. Oridonin attenuates the release of pro-inflammatory cytokines in lipopolysaccharide-induced RAW264.7 cells and acute lung injury. Oncotarget 8 (40): 68153–68164. https://doi.org/10.18632/oncotarget.19249.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Nicholas, Courtney, Sanjay Batra, Melissa A. Vargo, Oliver H. Voss, Mikhail A. Gavrilin, Mark D. Wewers, Denis C. Guttridge, Erich Grotewold, and Andrea I. Doseff. 2007. Apigenin blocks lipopolysaccharide-induced lethality in vivo and proinflammatory cytokines expression by inactivating NF-κB through the suppression of p65 phosphorylation. Journal of Immunology 179 (10): 7121–7127. https://doi.org/10.4049/jimmunol.179.10.7121.

    Article  CAS  Google Scholar 

  18. Mueller, M.D., D.I. Lebovic, E. Garrett, and R.N. Taylor. 2000. Neutrophils infiltrating the endometrium express vascular endothelial growth factor: potential role in endometrial angiogenesis. Fertility & Sterility 74 (1): 107–112. https://doi.org/10.1016/S0015-0282(00)00555-0.

    Article  CAS  Google Scholar 

  19. Borregaard, N., O.E. Sorensen, and K. Theilgaard-Monch. 2007. Neutrophil granules: a library of innate immunity proteins. Trends in Immunology 28 (8): 340–345. https://doi.org/10.1016/j.it.2007.06.002.

    Article  CAS  PubMed  Google Scholar 

  20. Salilew-Wondim, D., S. Ibrahim, S. Gebremedhn, D. Tesfaye, M. Heppelmann, H. Bollwein, C. Pfarrer, E. Tholen, C. Neuhoff, K. Schellander, and M. Hoelker. 2016. Clinical and subclinical endometritis induced alterations in bovine endometrial transcriptome and miRNome profile. BMC Genomics 17: 218. https://doi.org/10.1186/s12864-016-2513-9.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Hailemariam, D., S. Ibrahim, M. Hoelker, M. Drillich, W. Heuwieser, C. Looft, M.U. Cinar, E. Tholen, K. Schellander, and D. Tesfaye. 2014. MicroRNA-regulated molecular mechanism underlying bovine subclinical endometritis. Reproduction, Fertility, and Development 26 (6): 898–913. https://doi.org/10.1071/rd13027.

    Article  CAS  PubMed  Google Scholar 

  22. Yu, J.H., L. Long, Z.X. Luo, L.M. Li, and J.R. You. 2016. Anti-inflammatory role of microRNA let-7c in LPS treated alveolar macrophages by targeting STAT3. Asian Pacific Journal of Tropical Medicine 9 (1): 72–75. https://doi.org/10.1016/j.apjtm.2015.12.015.

    Article  CAS  PubMed  Google Scholar 

  23. Jiang, R., Y. Li, A. Zhang, B. Wang, Y. Xu, W. Xu, Y. Zhao, F. Luo, and Q. Liu. 2014. The acquisition of cancer stem cell-like properties and neoplastic transformation of human keratinocytes induced by arsenite involves epigenetic silencing of let-7c via Ras/NF-kappaB. Toxicology Letters 227 (2): 91–98. https://doi.org/10.1016/j.toxlet.2014.03.020.

    Article  CAS  PubMed  Google Scholar 

  24. Mitin, N., A.J. Kudla, S.F. Konieczny, and E.J. Taparowsky. 2001. Differential effects of Ras signaling through NFkappaB on skeletal myogenesis. Oncogene 20 (11): 1276–1286. https://doi.org/10.1038/sj.onc.1204223.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

Thank all members in the Laboratory of Veterinary Clinical Diagnosis with all the helpful suggestions. We especially thank Dr. Aftab Shaukat for English language editing.

Funding

This work was supported by the National Natural Science Foundation of China (Grant No. 31772816).

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Correspondence to Ganzhen Deng.

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The authors declare that they have no conflict of interest.

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Zhao, G., Zhang, T., Wu, H. et al. MicroRNA let-7c Improves LPS-Induced Outcomes of Endometritis by Suppressing NF-κB Signaling. Inflammation 42, 650–657 (2019). https://doi.org/10.1007/s10753-018-0922-4

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