Advertisement

Oleanolic acid attenuated diabetic mesangial cell injury by activation of autophagy via miRNA-142-5p/PTEN signaling

  • Juan Chen
  • Yumei Cui
  • Ning Zhang
  • Xiaoming Yao
  • Zhiguo Wang
  • Lin YangEmail author
Original Article
  • 27 Downloads

Abstract

Oleanolic acid (OA), a potential drug for diabetic nephropathy (DN) treatment was found to downregulate the expression of microRNA (miR). The research aimed to investigate the effect of OA on autophagy mediated through miR-142-5p targeted PTEN signal. NRK-52E cells were cultured under normal or high glucose condition. DN model were induced by intravenous injection with streptozotocin (55 mg/kg). Renal fibrosis mice were detected by hematoxylin and eosin (HE) staining, Masson staining and immunohistochemistry assay. TargetScan and dual-luciferase reporter assay system was used to detect the target of miR-142-5p. Expression levels of microRNA and proteins were analyzed by real-time PCR and western blotting. Autophagy was decreased in the progression of renal fibrosis in diabetic nephropathy mice (in vivo) and in high glucose-induced NRK-52E cells (rat kidney epithelial cells) (in vitro) as the expression ofLC-3I and LC-3II (indicators of autophagy) were decreased mice MiR-142-5p was unregulated and PTEN was down-regulated in kidney mice and high glucose-induced NRK-52E cells. Targetscan prediction revealed that PTEN was a target of miR-142-5p. OA restricted HG-induced NRK-52E cell fibrosis through inhibition of miR-142-5p to promote PTEN expression and autophagy levels. To sum up, the research indicated that OA promoted autophagy through inhibition of PI3K/AKT/mTOR pathway. OA alleviated diabetic renal fibrosis by increasing autophagy through regulation of miR-142-5p/PTEN via PI3K/AKT/mTOR pathway in NRK-52E cells.

Keywords

Oleanolic acid Diabetic nephropathy miR-142 Autophagy 

Notes

Acknowledgements

Not applicable.

Funding

None.

Compliance with ethical standards

Competing interests

The authors declare that they have no competing interests, and all authors should confirm its accuracy.

References

  1. Bai X, Zhou Y, Yang M (2017) MicroRNA-142-5p induces cancer stem cell-like properties of cutaneous squamous cell carcinoma via inhibiting PTEN. J Cell Biochemis 119:2179–2188CrossRefGoogle Scholar
  2. Carnero A, Blanco-Aparicio C, Renner O, Link W, Leal JF (2008) The PTEN/PI3K/AKT signalling pathway in cancer, therapeutic implications. Curr Cancer Drug Targets 8:187–198CrossRefGoogle Scholar
  3. Castellano JM, Angeles G, Teresa D, Mirela R, Cayuela JA (2013) Biochemical basis of the antidiabetic activity of oleanolic acid and related pentacyclic triterpenes. Diabetes 62:1791–1799CrossRefGoogle Scholar
  4. Chen S, Wen X, Zhang W, Wang C, Liu J, Liu C (2017) Hypolipidemic effect of oleanolic acid is mediated by the miR-98-5p/PGC-1β axis in high-fat diet-induced hyperlipidemic mice. FASEB J 31:1085CrossRefGoogle Scholar
  5. Delić D et al (2016) Urinary exosomal miRNA signature in type II diabetic nephropathy patients. PLoS ONE 11:e0150154CrossRefGoogle Scholar
  6. Ding Y, Choi ME (2015) Autophagy in diabetic nephropathy. J Endocrinol 224:R15CrossRefGoogle Scholar
  7. Du J et al (2015) MicroRNA-451 regulates stemness of side population cells via PI3K/Akt/mTOR signaling pathway in multiple myeloma. Oncotarget 6:14993–15007Google Scholar
  8. Kainz A et al (2015) Prediction of prevalence of chronic kidney disease in diabetic patients in countries of the European Union up to 2025. Nephrol Dial Transplant 30:iv113CrossRefGoogle Scholar
  9. Li XU, Wang C (2018) Research progress and prospect of oleanolic acid in treatment of diabetes. Chinese J Exp Trad Med Formul 24:228–234Google Scholar
  10. Lim AKH (2014) Diabetic nephropathy—complications and treatment. Int J Nephrol Renovasc Dis 7:361–381CrossRefGoogle Scholar
  11. Lit YZ, Meyer T (2006) Managing diabetic nephropathy: recent studies. Curr Opin Nephrol Hypertens 15:111–116Google Scholar
  12. Mitchell F (2012) Diabetes: PTEN mutations increase insulin sensitivity and obesity. Nat Rev Endocrinol 8:698CrossRefGoogle Scholar
  13. Mukundwa A, Langa SO, Mukaratirwa S, Masola B (2016) In vivo effects of diabetes, insulin and oleanolic acid on enzymes of glycogen metabolism in the skin of streptozotocin-induced diabetic male Sprague-Dawley rats. Biochem Biophys Res Commun 471:315–319CrossRefGoogle Scholar
  14. Ngubane PS, Bubuya M, Musabayane CT (2011) The effects of Syzygium aromaticum-derived oleanolic acid on glycogenic enzymes in streptozotocin-induced diabetic rats. Ren Fail 33:434–439CrossRefGoogle Scholar
  15. Pollier J, Goossens A (2012) Oleanolic acid. Phytochemistry 77:10–15CrossRefGoogle Scholar
  16. Qi W (2003) The present situation of TCM treatment for diabetes and its researches. J Trad Chin Med 23:67–73Google Scholar
  17. Tanaka Y, Kume S, Kitada M, Kanasaki K, Uzu T, Maegawa H, Koya D (2012) Autophagy as a therapeutic target in diabetic nephropathy. J Diabetes Res 2012:628978Google Scholar
  18. Vasiliki M et al (2013) Losartan affects glomerular AKT and mTOR phosphorylation in an experimental model of type 1 diabetic nephropathy. J Histochem Cytochemis 61:433–443CrossRefGoogle Scholar
  19. Xia C, Liang S, He Z, Zhu X, Chen R, Chen J (2018) Metformin, a first-line drug for type 2 diabetes mellitus, disrupts the MALAT1/miR-142-3p sponge to decrease invasion and migration in cervical cancer cells. Eur J Pharmacol 830:59–67CrossRefGoogle Scholar
  20. Xu W, Wang W (2018) MicroRNA-142-5p modulates breast cancer cell proliferation and apoptosis by targeting phosphatase and tensin homolog. Mol Med Rep 17:7529–7536Google Scholar
  21. Xu XH et al (2017) Resveratrol transcriptionally regulates miRNA-18a-5p expression ameliorating diabetic nephropathy via increasing autophagy. Eur Rev Med Pharmacol Sci 21:4952–4965Google Scholar
  22. Zhu H, Leung SW (2015) Identification of microRNA biomarkers in type 2 diabetes: a meta-analysis of controlled profiling studies. Diabetologia 58:900–911CrossRefGoogle Scholar
  23. Zhu L, Zhao S, Liu S, Liu Q, Li F, Hao J (2016) PTEN regulates renal extracellular matrix deposit via increased CTGF in diabetes mellitus. J Cell Biochem 117:1187–1198CrossRefGoogle Scholar

Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  • Juan Chen
    • 1
  • Yumei Cui
    • 2
  • Ning Zhang
    • 3
  • Xiaoming Yao
    • 1
  • Zhiguo Wang
    • 1
  • Lin Yang
    • 4
    Email author
  1. 1.Department of Clinical Laboratory, Affiliated Hospital of Integrated Traditional Chinese and Western MedicineNanjing University of Chinese MedicineNanjingChina
  2. 2.Department of ENT, BenQ Medical CenterThe Affiliated BenQ Hospital of Nanjing, Medical UniversityNanjingChina
  3. 3.Department of Paediatrics, Zhong Da HospitalMedical School of Southeast UniversityNanjingChina
  4. 4.Department of Special Diagnosis DepartmentPLA 81st HospitalNanjingChina

Personalised recommendations