The lncRNA OIP5-AS1/miR-181a-5p Axis Promotes TGF-β1-induced Fibrosis in HK2 Cells

Authors

  • Xiaoyan Li epartment of Endocrinology, Ganzhou People’s Hospital, Ganzhou, Jiangxi, China. Author
  • Hongxia Peng Department of Nephrology, Ganzhou People’s Hospital, Ganzhou, Jiangxi, China. Author
  • Qing Feng Department of Central laboratory, Ganzhou People’s Hospital, Ganzhou, Jiangxi, China. Author
  • Shumei Zhong Department of Endocrinology, Ganzhou People’s Hospital, Ganzhou, Jiangxi, China. Author
  • Yi Li Department of Endocrinology, Ganzhou People’s Hospital, Ganzhou, Jiangxi, China. Author
  • Yingling Zheng Department of Endocrinology, Ganzhou People’s Hospital, Ganzhou, Jiangxi, China. Author
  • Guang Yang Department of Nephrology, Ganzhou People’s Hospital, Ganzhou, Jiangxi, China . Author

DOI:

https://doi.org/10.52547/7wk1jf85

Keywords:

HK2 cells, TGF-β, Fibrosis, OIP5-AS1

Abstract

Introduction. Th is study was conducted to explore the role of OIP5-AS1 in a fibrosis cell model through its interaction with miR-181a-5p.

Methods. An in-vitro fibrosis model was established by inducing human renal tubular epithelial cells (HK2) with TGF-β1. The expression levels of OIP5-AS1 and miR-181a-5p in the control (Normal) and model (TGF-β1) groups were measured using Quantitative Real-time Polymerase Chain Reaction (qPCR).. qPCR and  Western Blot  (WB) were used to detect the expression of genes and proteins related to fibrosis and EMT in the two groups of cells. Subsequently, The effect of OIP5-AS1 on TGF-β1-induced fibrosis in HK2 cells was investigated by assessing cell proliferation using the CCK-8 assay and analyzing the expression of fibrosis- and EMT-related proteins through WB.. The targeting relationship between OIP5-AS1 and miR-181a-5p, as well as the influence of OIP5-AS1 on miR-181a-5p expression, was investigated using a dual-luciferase reporter assay. Subsequently, the impact of miR-181a-5p upregulation on the proliferation of TGF-β1-induced HK2 cells was examined through a CCK-8 assay.

Results. The study found that TGF-β1 treatment upregulated OIP5-AS1, α-SMA, Col-IV, and FN in HK2 cells while downregulating miR-181a-5p and E-cadherin. OIP5-AS1 downregulation promoted cell proliferation and inhibited fibrosis-related proteins. MiR-181a-5p was identified as a direct target of OIP5-AS1, and its upregulation enhanced cell proliferation.

Conclusion . The suppression of OIP5-AS1 attenuates TGF-β1-induced fibrosis in HK2 cells through the regulation of miR-181a-5p.

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References

1. Bommer C, Heesemann E, Sagalova V, et al. The global economic burden of diabetes in adults aged 20-79 years: a cost-of-illness study. Lancet Diabetes Endocrinol. 2017 Jun;5(6):423-430.

2. Ahmad E, Lim S, Lamptey R, Webb DR, Davies MJ. Type 2 diabetes. Lancet. 2022 Nov 19;400(10365):1803-1820.

3. Vaz de Castro PAS, Bitencourt L, de Oliveira Campos JL, et al. Nephrogenic diabetes insipidus: a comprehensive overview. J Pediatr Endocrinol Metab. 2022 Feb

11;35(4):421-434.

4. Martínez-Arias L, Panizo S, Alonso-Montes C, et al. Effects of calcitriol and paricalcitol on renal fibrosis in CKD. Nephrol Dial Transplant. 2021 Apr 26;36(5):793-803.

5. Olmos G, Muñoz-Félix JM, Mora I, et al. Impaired erythropoietin synthesis in chronic kidney disease is caused by alterations in extracellular matrix composition. J Cell Mol Med. 2018 Jan;22(1):302-314.

6. Chang FC, Chou YH, Chen YT, Lin SL. Novel insights into pericyte-myofibroblast transition and therapeutic targets in renal fibrosis. J Formos Med Assoc, 2012. 111(11): p.

589- 98.

7. Jung GS, Hwang YJ, Choi JH, Lee KM. Lin28a attenuates TGF-β-induced renal fibrosis. BMB Rep, 2020. 53(11): p.

594- 599.

8. Robinson, E.K., S. Covarrubias, and S. Carpenter. The how and why of lncRNA function: An innate immune perspective. Biochim Biophys Acta Gene Regul Mech, 2020. 1863(4): p. 194419.

9. Zhang W, Tang G, Zhou S, Niu Y. LncRNA-miRNA interaction prediction through sequence-derived linear neighborhood propagation method with information combination. BMC Genomics, 2019. 20(Suppl 11): p. 946.

10. Zhuo LA, Wen YT, Wang Y, et al. LncRNA SNHG8 is identified as a key regulator of acute myocardial infarction by RNA-seq analysis. Lipids Health Dis, 2019. 18(1): p. 201.

11. Wang L, Cho KB, Li Y, et al. Long Noncoding RNA

(lncRNA)-Mediated Competing Endogenous RNA Networks Provide Novel Potential Biomarkers and Therapeutic Targets for Colorectal Cancer. Int J Mol Sci, 2019. 20(22).

12. Huang Z, Ye B, Wang Z, et al. Inhibition of LncRNA-HRIM Increases Cell Viability by Regulating Autophagy Levels During Hypoxia/Reoxygenation in Myocytes. Cell Physiol Biochem, 2018. 46(4): p. 1341-1351.

13. Zhang K, Zhang M, Yao Q, et al. The hepatocyte- specifically expressed lnc-HSER alleviates hepatic fibrosis by inhibiting hepatocyte apoptosis and epithelial-mesenchymal transition. Theranostics, 2019. 9(25): p. 7566-7582.

14. Liu H, Wang B, Zhang J, et al. A novel lnc-PCF promotes the proliferation of TGF-β1-activated epithelial cells by targeting miR-344a-5p to regulate map3k11 in pulmonary fibrosis. Cell Death Dis, 2017. 8(10): p. e3137.

15. Chen, B. The miRNA-184 drives renal fibrosis by targeting HIF1AN in vitro and in vivo. Int Urol Nephrol, 2019. 51(3):

p. 543-550.

16. Wang Z, Chen Z, Li B, et al. Curcumin attenuates

renal interstitial fibrosis of obstructive nephropathy by suppressing epithelial-mesenchymal transition through inhibition of the TLR4/NF-кB and PI3K/AKT signalling pathways. Pharm Biol, 2020. 58(1): p. 828-837.

17. Guo, J. Effect of miR-21 on Renal Fibrosis Induced by Nano-SiO2 in Diabetic Nephropathy Rats via PTEN/AKT Pathway. J Nanosci Nanotechnol, 2021. 21(2): p. 1079-1084.

18. Wang W, Jia YJ, Yang YL, et al. LncRNA GAS5 exacerbates renal tubular epithelial fibrosis by acting as a competing endogenous RNA of miR-96-5p. Biomed Pharmacother, 2020. 121: p. 109411.

19. Ge Y, Wang J, Wu D, et al. lncRNA NR_038323 Suppresses Renal Fibrosis in Diabetic Nephropathy by Targeting the miR-324-3p/DUSP1 Axis. Mol Ther Nucleic Acids, 2019. 17: p. 741-753.

20. Wang LW, Li XB, Liu Z, et al. Long non-coding RNA OIP5-AS1 promotes proliferation of gastric cancer cells by targeting miR-641. Eur Rev Med Pharmacol Sci, 2019. 23(24): p. 10776-10784.

21. Deng J, Deng H, Liu C, Liang Y, Wang S. Long non-coding RNA OIP5-AS1 functions as an oncogene in lung adenocarcinoma through targeting miR-448/Bcl-2. Biomed Pharmacother, 2018. 98: p. 102-110.

22. Song L, Zhou Z, Gan Y, et al. Long noncoding RNA OIP5-AS1 causes cisplatin resistance in osteosarcoma through inducing the LPAATβ/PI3K/AKT/mTOR signaling pathway by sponging the miR-340-5p. J Cell Biochem, 2019. 120(6): p. 9656-9666.

23. Yang S, Wu H, Li Y, et al. Inhibition of PFKP in renal tubular epithelial cell restrains TGF-β induced glycolysis and renal fibrosis. Cell Death Dis. 2023 Dec 12;14(12):p. 816.

24. Liu Y, Bi X, Xiong J, et al. MicroRNA-34a Promotes Renal Fibrosis by Downregulation of Klotho in Tubular Epithelial Cells. Mol Ther. 2019 May 8;27(5):p. 1051-1065.

25. Li W, Li N, Shi K, Chen Q. Systematic review and meta-analysis of the utility of long non-coding RNA GAS5 as a diagnostic and prognostic cancer biomarker. Oncotarget, 2017. 8(39): p. 66414-66425.

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Published

2025-05-16

Issue

Section

ORIGINAL | Kidney Diseases

How to Cite

The lncRNA OIP5-AS1/miR-181a-5p Axis Promotes TGF-β1-induced Fibrosis in HK2 Cells. (2025). Iranian Journal of Kidney Diseases, 19(02), 97-105. https://doi.org/10.52547/7wk1jf85

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