Skip to main content

Advertisement

SpringerLink
Log in

Protection of tubular epithelial cells during renal injury via post-transcriptional control of BMP7

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

Severe injury of renal tubular epithelial cells may cause acute renal failure, the progression of which results in renal fibrosis, and obstructive nephropathy. Transforming growth factor β 1 and bone morphogenic protein 7 (BMP7) play contradicting roles in and coordinate the process of epithelial-to-mesenchymal transition of renal tubular epithelial cells, but the molecular regulation of BMP7 remains ill-defined. Here, we addressed this question. We found that after induction of unilateral ureteral obstruction (UUO) in mice, the increases in BMP7 mRNA were much more pronounced than BMP7 protein in kidney, suggesting the presence of post-transcriptional control of BMP7. Moreover, significant increases in a BMP7-targeting microRNA, miR-384-5p, were detected in the mouse kidney post UUO. Overexpression of miR-384-5p significantly decreased BMP7 protein, while depletion of miR-384-5p significantly increased BMP7 protein in renal epithelial cells. Bioinformatics study showed that miR-384-5p appeared to suppress BMP7 protein translation, through its direct binding to the 3′-UTR of BMP7 mRNA. Furthermore, suppression of miR-384-5p in vivo attenuated severity of renal injury by UUO. Together, our study sheds light on miR-384-5p as a crucial factor that regulates the fibrosis-related pathogenesis after renal injury, and points to miR-384-5p as a promising innovative therapeutic target for prevention of renal fibrosis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Yang B, Chen S, Wu M, Zhang L, Ruan M, Chen X, Chen Z, Mei C, Mao Z (2017) PHF14: an innate inhibitor against the progression of renal fibrosis following folic acid-induced kidney injury. Sci Rep 7:39888. doi:10.1038/srep39888

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Liang H, Ma Z, Peng H, He L, Hu Z, Wang Y (2016) CXCL16 deficiency attenuates renal injury and fibrosis in salt-sensitive hypertension. Sci Rep 6:28715. doi:10.1038/srep28715

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Aggarwal S, Grange C, Iampietro C, Camussi G, Bussolati B (2016) Human CD133+ renal progenitor cells induce erythropoietin production and limit fibrosis after acute tubular injury. Sci Rep 6:37270. doi:10.1038/srep37270

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Kaissling B, Lehir M, Kriz W (2013) Renal epithelial injury and fibrosis. Biochim Biophys Acta 1832:931–939. doi:10.1016/j.bbadis.2013.02.010

    Article  CAS  PubMed  Google Scholar 

  5. Godin RE, Takaesu NT, Robertson EJ, Dudley AT (1998) Regulation of BMP7 expression during kidney development. Development 125:3473–3482

    CAS  PubMed  Google Scholar 

  6. Zeisberg M, Hanai J, Sugimoto H, Mammoto T, Charytan D, Strutz F, Kalluri R (2003) BMP-7 counteracts TGF-beta1-induced epithelial-to-mesenchymal transition and reverses chronic renal injury. Nat Med 9:964–968. doi:10.1038/nm888

    Article  CAS  PubMed  Google Scholar 

  7. Pan B, Liu G, Jiang Z, Zheng D (2015) Regulation of renal fibrosis by macrophage polarization. Cell Physiol Biochem 35:1062–1069. doi:10.1159/000373932

    Article  CAS  PubMed  Google Scholar 

  8. Wang S, Hirschberg R (2003) BMP7 antagonizes TGF-beta-dependent fibrogenesis in mesangial cells. Am J Physiol Renal Physiol 284:F1006–F1013. doi:10.1152/ajprenal.00382.2002

    Article  CAS  PubMed  Google Scholar 

  9. Buijs JT, Henriquez NV, van Overveld PG, van der Horst G, ten Dijke P, van der Pluijm G (2007) TGF-beta and BMP7 interactions in tumour progression and bone metastasis. Clin Exp Metastasis 24:609–617. doi:10.1007/s10585-007-9118-2

    Article  CAS  PubMed  Google Scholar 

  10. Fuchshofer R, Stephan DA, Russell P, Tamm ER (2009) Gene expression profiling of TGFβ2- and/or BMP7-treated trabecular meshwork cells: identification of Smad7 as a critical inhibitor of TGF-β2 signaling. Exp Eye Res 88:1020–1032. doi:10.1016/j.exer.2009.01.002

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Khan I, Agarwal P, Thangjam GS, Radhesh R, Rao SG, Kondaiah P (2011) Role of TGF-β and BMP7 in the pathogenesis of oral submucous fibrosis. Growth Factors 29:119–127. doi:10.3109/08977194.2011.582839

    Article  CAS  PubMed  Google Scholar 

  12. Goto Y, Kurozumi A, Nohata N, Kojima S, Matsushita R, Yoshino H, Yamazaki K, Ishida Y, Ichikawa T, Naya Y, Seki N (2016) The microRNA signature of patients with sunitinib failure: regulation of UHRF1 pathways by microRNA-101 in renal cell carcinoma. Oncotarget 7:59070–59086. doi:10.18632/oncotarget.10887

    Article  PubMed  PubMed Central  Google Scholar 

  13. Hou X, Tian J, Geng J, Li X, Tang X, Zhang J, Bai X (2016) MicroRNA-27a promotes renal tubulointerstitial fibrosis via suppressing PPARgamma pathway in diabetic nephropathy. Oncotarget 7:47760–47776. doi:10.18632/oncotarget.10283

    Article  PubMed  PubMed Central  Google Scholar 

  14. Wang B, Yao K, Huuskes BM, Shen HH, Zhuang J, Godson C, Brennan EP, Wilkinson-Berka JL, Wise AF, Ricardo SD (2016) Mesenchymal Stem cells deliver exogenous microRNA-let7c via exosomes to attenuate renal fibrosis. Mol Ther 24:1290–1301. doi:10.1038/mt.2016.90

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Lv LL, Cao YH, Ni HF, Xu M, Liu D, Liu H, Chen PS, Liu BC (2013) MicroRNA-29c in urinary exosome/microvesicle as a biomarker of renal fibrosis. Am J Physiol Renal Physiol 305:F1220–F1227. doi:10.1152/ajprenal.00148.2013

    Article  CAS  PubMed  Google Scholar 

  16. Di Leva G, Croce CM (2013) miRNA profiling of cancer. Curr Opin Genet Dev 23:3–11. doi:10.1016/j.gde.2013.01.004

    Article  PubMed  PubMed Central  Google Scholar 

  17. Pereira DM, Rodrigues PM, Borralho PM, Rodrigues CM (2013) Delivering the promise of miRNA cancer therapeutics. Drug Discov Today 18:282–289. doi:10.1016/j.drudis.2012.10.002

    Article  CAS  PubMed  Google Scholar 

  18. Mei Q, Li F, Quan H, Liu Y, Xu H (2014) Busulfan inhibits growth of human osteosarcoma through miR-200 family microRNAs in vitro and in vivo. Cancer Sci 105:755–762. doi:10.1111/cas.12436

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Wang F, Xiao W, Sun J, Han D, Zhu Y (2014) miRNA-181c inhibits EGFR-signaling-dependent MMP9 activation via suppressing Akt phosphorylation in glioblastoma. Tumour Biol 35:8653–8658. doi:10.1007/s13277-014-2131-6

    Article  CAS  PubMed  Google Scholar 

  20. Liu G, Jiang C, Li D, Wang R, Wang W (2014) miRNA-34a inhibits EGFR-signaling-dependent MMP7 activation in gastric cancer. Tumour Biol 35:9801–9806. doi:10.1007/s13277-014-2273-6

    Article  CAS  PubMed  Google Scholar 

  21. Bao Y, Lin C, Ren J, Liu J (2013) MicroRNA-384-5p regulates ischemia-induced cardioprotection by targeting phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit delta (PI3K p110delta). Apoptosis 18:260–270. doi:10.1007/s10495-013-0802-1

    Article  CAS  PubMed  Google Scholar 

  22. Liu CG, Wang JL, Li L, Wang PC (2014) MicroRNA-384 regulates both amyloid precursor protein and β-secretase expression and is a potential biomarker for Alzheimer’s disease. Int J Mol Med 34:160–166. doi:10.3892/ijmm.2014.1780

    Article  PubMed  Google Scholar 

  23. Wen JG (2002) Partial unilateral ureteral obstruction in rats. Neurourol Urodyn 21:231–250

    Article  PubMed  Google Scholar 

  24. Martina MN, Bandapalle S, Rabb H, Hamad AR (2014) Isolation of double negative alphabeta T cells from the kidney. J Vis Exp. doi:10.3791/51192

    PubMed  PubMed Central  Google Scholar 

  25. Chen YS, Mathias RA, Mathivanan S, Kapp EA, Moritz RL, Zhu HJ, Simpson RJ (2011) Proteomics profiling of Madin-Darby canine kidney plasma membranes reveals Wnt-5a involvement during oncogenic H-Ras/TGF-beta-mediated epithelial-mesenchymal transition. Mol Cell Proteomics 10(M110):001131. doi:10.1074/mcp.M110.001131

    PubMed  Google Scholar 

  26. Wang S, Meng XM, Ng YY, Ma FY, Zhou S, Zhang Y, Yang C, Huang XR, Xiao J, Wang YY, Ka SM, Tang YJ, Chung AC, To KF, Nikolic-Paterson DJ, Lan HY (2016) TGF-β/Smad3 signalling regulates the transition of bone marrow-derived macrophages into myofibroblasts during tissue fibrosis. Oncotarget 7:8809–8822. doi:10.18632/oncotarget.6604

    Article  PubMed  Google Scholar 

Download references

Acknowledgement

The study was supported by the National Natural Foundation Self-support Program (No. 81200528).

Author information

Authors and Affiliations

  1. Department of Nephrology, The First Affiliated Hospital of Medical College of Xi’an Jiaotong University, 227 Yantaxi Road, Xi’an, 710061, China

    Jiping Sun, Aiping Yin, Fei Zhao, Wenjing Zhang, Jia Lv & Jing Lv

Authors
  1. Jiping Sun
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Aiping Yin
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Fei Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Wenjing Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jia Lv
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jing Lv
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jiping Sun.

Ethics declarations

Conflict of interest

The authors have declared that no competing interests exist.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sun, J., Yin, A., Zhao, F. et al. Protection of tubular epithelial cells during renal injury via post-transcriptional control of BMP7. Mol Cell Biochem 435, 141–148 (2017). https://doi.org/10.1007/s11010-017-3063-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11010-017-3063-4

Keywords

Search

Navigation