pp 1–11 | Cite as

Inhibiting microRNA-7 Expression Exhibited a Protective Effect on Intestinal Mucosal Injury in TNBS-Induced Inflammatory Bowel Disease Animal Model

  • Jing Guo
  • Li-juan Yang
  • Mei Sun
  • Ling-fen XuEmail author
Original Article


This study aimed to explore the expression and correlation of microRNA-7 (miR-7) and trefoil factor 3 (TFF3) genes and proteins in inflammatory bowel disease (IBD) mouse models and to elucidate the effect of miR-7 inhibition in the intestinal mucosa in IBD models. A TNBS-induced IBD mouse model was established. Changes in intestinal inflammation were observed by HE staining, and the expression levels of miR-7 and TFF3 were detected by RT-PCR. After miRNA-antagomir injection, the degree of colonic tissue damage and the expression levels of miR-7 and TFF3 in intestinal tissues were compared. TNBS-induced IBD mice showed significant weight loss, significantly decreased disease activity index (DAI), and a significantly increased pathological damage score. miR-7 was highly expressed in the colon tissue of IBD mice, and TFF3 was downregulated. Inhibition of the expression of miR-7 improved the stool characteristics and fecal occult blood (OB) of IBD mice, significantly increased the expression of TFF3 protein, and decreased the pathological damage scores. In the IBD mouse model, miR-7 posttranscriptionally regulates TFF3. The inhibition of miR-7 expression improves some clinical manifestations of IBD mice, reduces the pathological damage of the intestinal mucosa, and shows a protective effect in IBD.


microRNA-7 trefoil factor 3 inflammatory bowel disease miRNA antagomir 


Funding Information

The present study was supported by grants from the National Natural Science Foundation of China Youth Foundation (grant no. 81400585) and the Natural Science Foundation of Liaoning Province, China (grant no. 2014021042).

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.


  1. 1.
    Henderson, P., and D.C. Wilson. 2012. The rising incidence of paediatric-onset inflammatory bowel disease. Archives of Disease in Childhood 97: 585–586. Scholar
  2. 2.
    Matsuoka, Y., J.C. Pascall, and K.D. Brown. 1999. Quantitative analysis reveals differential expression of mucin (muc2) and intestinal trefoil factor mRNAs along the longitudinal axis of rat intestine. Biochimica et Biophysica Acta 1489: 336–344. Scholar
  3. 3.
    Bartel, D.P. 2004. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116: 281–297.CrossRefGoogle Scholar
  4. 4.
    Friedman, R.C., K.K. Farh, C.B. Burge, and D.P. Bartel. 2009. Most mammalian mRNAs are conserved targets of microRNAs. Genome Research 19: 92–105. Scholar
  5. 5.
    O’Connell, R.M., D.S. Rao, and D. Baltimore. 2012. microRNA regulation of inflammatory responses. Annual Review of Immunology 30: 295–312. Scholar
  6. 6.
    Coskun, M., J.T. Bjerrum, J.B. Seidelin, and O.H. Nielsen. 2012. MicroRNAs in inflammatory bowel disease-pathogenesis, diagnostics and therapeutics. World Journal of Gastroenterology 18: 4629–4634. Scholar
  7. 7.
    Guo, J., M. Sun, X. Teng, and L.F. Xu. 2008. MicroRNA-7-5p regulates the expression of TFF3 in inflammatory bowel disease. Molecular Medicine Reports 16: 1200–1206. Scholar
  8. 8.
    Teng, X., L.F. Xu, and M. Sun. 2009. Effects of trefoil peptide 3 on expression of TNF-α, TLR4, and NF-κB in trinitrobenzene sulphonic acid induced colitis mice. Inflammation 32: 120–129. Scholar
  9. 9.
    Fitzpatrick, L.R., K. Meirelles, J.S. Small, F.J. Puleo, W.A. Koltun, and R.N. Cooney. 2010. A new model of chronic hapten-induced colitis in young rats. Journal of Pediatric Gastroenterology and Nutrition 50: 240–250. Scholar
  10. 10.
    Khounlotham, M., W. Kim, E. Peatman, P. Nava, O. Medina-Contreras, C. Addis, S. Koch, B. Fournier, A. Nusrat, T.L. Denning, et al. 2012. Compromised intestinal epithelial barrier induces adaptive immune compensation that protects from colitis. Immunity 37: 563–573. Scholar
  11. 11.
    Wang, X.Q., Y. Zhang, C.D. Xu, L.R. Jiang, Y. Huang, H.M. Du, and X.J. Wang. 2013. Inflammatory bowel disease in Chinese children: a multicenter analysis over a decade from Shanghai. Inflammatory Bowel Diseases 19: 423–428. Scholar
  12. 12.
    Fang, Y., J.L. Xue, Q. Shen, J. Chen, and L. Tian. 2012. MicroRNA-7 inhibits tumor growth and metastasis by targeting the phosphoinositide 3-kinase/Akt pathway in hepatocellular carcinoma. Hepatology 55: 1852–1862. Scholar
  13. 13.
    Xu, K., J. Chen, C. Qin, and X. Song. 2014. miR-7 inhibits colorectal cancer cell proliferation and induces apoptosis by targeting XRCC2. OncoTargets and Therapy 7: 325–332. Scholar
  14. 14.
    Guo, J., L.F. Xu, X. Teng, and M. Sun. 2017. MicroRNA-7-5p regulates the proliferation and migration of intestinal epithelial cells by targeting trefoil factor 3 via inhibiting the phosphoinositide 3-kinase/Akt signalling pathway. International Journal of Molecular Medicine 40: 1435–1443. Scholar
  15. 15.
    Xu, L.F., X. Teng, J. Guo, and M. Sun. 2012. Protective effect of intestinal trefoil factor on injury of intestinal epithelial tight junction induced by platelet activating factor. Inflammation 35: 308–315. Scholar
  16. 16.
    Xu, L.F., C. Xu, Z.Q. Mao, X. Teng, L. Ma, and M. Sun. 2011. Disruption of the F-actin cytoskeleton and monolayer barrier integrity induced by PAF and the protective effect of ITF on intestinal epithelium. Archives of Pharmacal Research 34: 245–251. Scholar
  17. 17.
    Lin, N., L.F. Xu, and M. Sun. 2013. The protective effect of trefoil factor 3 on the intestinal tight junction barrier is mediated by toll-like receptor 2 via a PI3K/Akt dependent mechanism. Biochemical and Biophysical Research Communications 440: 143–149. Scholar
  18. 18.
    Wang, M., H. Gu, H. Qian, W. Zhu, C. Zhao, X. Zhang, Y. Tao, L. Zhang, and W. Xu. 2013. miR-17-5p/20a are important markers for gastric cancer and murine double minute 2 participates in their functional regulation. European Journal of Cancer 49: 2010–2021. Scholar
  19. 19.
    Lu, Y., Y. Zhang, N. Wang, Z. Pan, X. GaoX, F. Zhang, Y. Zhang, H. Shan, X. Luo, Y. Bai, et al. 2010. MicroRNA-328 contributes to adverse electrical remodeling in atrial fibrillation. Circulation 122: 2378–2387. Scholar
  20. 20.
    Huang, Y., J. Hong, S. Zheng, Y. Ding, S. Guo, H. Zhang, X. Zhang, Q. Du, and Z. Liang. 2011. Elimination pathways of systemically delivered siRNA. Molecular Therapy 219: 381–385. Scholar
  21. 21.
    Liu, W., Y. Zhang, P. Xia, S. Li, X. Feng, Y. Gao, K. Wang, Y. Song, Z. Duan, S. Yang, et al. 2016. MicroRNA-7 regulates IL-1β-induced extracellular matrix degeneration by targeting GDF5 in human nucleus pulposus cells. Biomedicine & Pharmacotherapy 83: 1414–1421. Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of PediatricsShengjing Hospital of China Medical UniversityShenyangPeople’s Republic of China
  2. 2.Dalian Children’s HospitalDalianPeople’s Republic of China

Personalised recommendations