Reduction in miRNA-125b-5p levels is associated with obstructive renal injury

Wang,Silu; Wu,Lianfeng; Du,Linyong; Lu,Hong; Chen,Bicheng; Bai,Yongheng

doi:10.3892/br.2017.875

Reduction in miRNA-125b-5p levels is associated with obstructive renal injury

Authors:
- Silu Wang
- Lianfeng Wu
- Linyong Du
- Hong Lu
- Bicheng Chen
- Yongheng Bai
View Affiliations

Affiliations: Key Laboratory of Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China, Department of Laboratory Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China, School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou, Zhejiang 325035, P.R. China
Published online on: March 17, 2017 https://doi.org/10.3892/br.2017.875
Pages: 449-454

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Obstructive renal injury is a common disease that leads to progressive glomerulosclerosis, tubulointerstitial fibrosis and loss of renal function. MicroRNAs (miRNAs/miRs) are small non-coding molecules that may be involved in the progression of many renal diseases. The aim of the present study was to investigate the roles of miRNAs, including miR‑125b, miR‑326 and miR‑324p, in obstructive renal injury. Blood samples were collected from 91 patients with ureteral obstruction and 76 controls to examine renal function. In addition, the levels of miR‑125b, miR‑326 and miR‑324p in patients with ureteral obstruction and controls were determined by the reverse transcription‑quantitative polymerase chain reaction. Furthermore, the relationship between miRNA levels and renal function was evaluated by the Mann‑Whitney U test. Upregulated levels of serum creatinine (SCr) in patients with ureteral obstruction were observed, identifying the injury of renal function. Although the expression levels of miR‑324‑5p [1.003 (0.391‑2.279) vs. 0.934 (0.579‑1.539), P=0.300] and miR‑326 [0.840 (0.180‑2.020) vs. 0.949 (0.507‑1.702), P=0.050] presented no significant difference, the levels of miR‑125b‑5p [0.755 (0.210‑2.110) vs. 0.960 (0.390‑1.770), P=0.002] in patients with ureteral obstruction were significantly lower than those in controls. These results indicated that there is a stronger correlation of miR‑125b‑5p with the occurrence of ureteral obstruction, especially for the female (P=0.0171) and elderly (P=0.0142). Furthermore, the levels of miR‑125b‑5p (r=‑0.175, P=0.038) were closely associated with the serum levels of SCr, suggesting a key role of miR‑125b‑5p in renal dysfunction. Thus, these findings suggested that miR‑125b‑5p in patients with ureteral obstruction correlated with renal function, and may be a potential biomarker for obstructive renal injury.

View Figures

View References

1	Dikmen B, Yagmurdur H, Akgul T, Astarci M, Ustun H and Germiyanoglu C: Preventive effects of propofol and ketamine on renal injury in unilateral ureteral obstruction. J Anesth. 24:73–80. 2010. View Article : Google Scholar : PubMed/NCBI
2	Ucero AC, Benito-Martin A, Izquierdo MC, Sanchez-Niño MD, Sanz AB, Ramos AM, Berzal S, Ruiz-Ortega M, Egido J and Ortiz A: Unilateral ureteral obstruction: Beyond obstruction. Int Urol Nephrol. 46:765–776. 2014. View Article : Google Scholar : PubMed/NCBI
3	Kinn AC and Bohman SO: Renal structural and functional changes after unilateral ureteral obstruction in rabbits. Scand J Urol Nephrol. 17:223–234. 1983. View Article : Google Scholar : PubMed/NCBI
4	Klahr S: New insights into the consequences and mechanisms of renal impairment in obstructive nephropathy. Am J Kidney Dis. 18:689–699. 1991. View Article : Google Scholar : PubMed/NCBI
5	Lee RC, Feinbaum RL and Ambros V: The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell. 75:843–854. 1993. View Article : Google Scholar : PubMed/NCBI
6	Glowacki F, Savary G, Gnemmi V, Buob D, van der Hauwaert C, Lo-Guidice JM, Bouyé S, Hazzan M, Pottier N, Perrais M, et al: Increased circulating miR-21 levels are associated with kidney fibrosis. PLoS One. 8:e580142013. View Article : Google Scholar : PubMed/NCBI
7	Sayed D and Abdellatif M: MicroRNAs in development and disease. Physiol Rev. 91:827–887. 2011. View Article : Google Scholar : PubMed/NCBI
8	Wang G, Kwan BC, Lai FM, Chow KM, Li PK and Szeto CC: Urinary miR-21, miR-29, and miR-93: Novel biomarkers of fibrosis. Am J Nephrol. 36:412–418. 2012. View Article : Google Scholar : PubMed/NCBI
9	Aguado-Fraile E, Ramos E, Conde E, Rodríguez M, Martín-Gómez L, Lietor A, Candela Á, Ponte B, Liaño F and García-Bermejo ML: A Pilot Study Identifying a Set of microRNAs As Precise Diagnostic Biomarkers of Acute Kidney Injury. PLoS One. 10:e01271752015. View Article : Google Scholar : PubMed/NCBI
10	Wang B, Komers R, Carew R, Winbanks CE, Xu B, Herman-Edelstein M, Koh P, Thomas M, Jandeleit-Dahm K, Gregorevic P, et al: Suppression of microRNA-29 expression by TGF-β1 promotes collagen expression and renal fibrosis. J Am Soc Nephrol. 23:252–265. 2012. View Article : Google Scholar : PubMed/NCBI
11	Aguado-Fraile E, Ramos E, Sáenz-Morales D, Conde E, Blanco-Sánchez I, Stamatakis K, del Peso L, Cuppen E, Brüne B and Bermejo ML: miR-127 protects proximal tubule cells against ischemia/reperfusion: Identification of kinesin family member 3B as miR-127 target. PLoS One. 7:e443052012. View Article : Google Scholar : PubMed/NCBI
12	Fan PC, Chen CC, Chen YC, Chang YS and Chu PH: MicroRNAs in acute kidney injury. Hum Genomics. 10:292016. View Article : Google Scholar : PubMed/NCBI
13	Liu Z, Wang S, Mi QS and Dong Z: MicroRNAs in Pathogenesis of Acute Kidney Injury. Nephron. 134:149–153. 2016. View Article : Google Scholar : PubMed/NCBI
14	Bai Y, Lu H, Lin C, Xu Y, Hu D, Liang Y, Hong W and Chen B: Sonic hedgehog-mediated epithelial-mesenchymal transition in renal tubulointerstitial fibrosis. Int J Mol Med. 37:1317–1327. 2016.PubMed/NCBI
15	Hu L, Lin X, Lu H, Chen B and Bai Y: An overview of hedgehog signaling in fibrosis. Mol Pharmacol. 87:174–182. 2015. View Article : Google Scholar : PubMed/NCBI
16	Bai Y, Lu H, Wu C, Liang Y, Wang S, Lin C, Chen B and Xia P: Resveratrol inhibits epithelial-mesenchymal transition and renal fibrosis by antagonizing the hedgehog signaling pathway. Biochem Pharmacol. 92:484–493. 2014. View Article : Google Scholar : PubMed/NCBI
17	Ferretti E, De Smaele E, Miele E, Laneve P, Po A, Pelloni M, Paganelli A, Di Marcotullio L, Caffarelli E, Screpanti I, et al: Concerted microRNA control of Hedgehog signalling in cerebellar neuronal progenitor and tumour cells. EMBO J. 27:2616–2627. 2008. View Article : Google Scholar : PubMed/NCBI
18	Zhang J, Na S, Liu C, Pan S, Cai J and Qiu J: MicroRNA-125b suppresses the epithelial-mesenchymal transition and cell invasion by targeting ITGA9 in melanoma. Tumour Biol. 37:5941–5949. 2016. View Article : Google Scholar : PubMed/NCBI
19	Zhou JN, Zeng Q, Wang HY, Zhang B, Li ST, Nan X, Cao N, Fu CJ, Yan XL, Jia YL, et al: MicroRNA-125b attenuates epithelial-mesenchymal transitions and targets stem-like liver cancer cells through small mothers against decapentaplegic 2 and 4. Hepatology. 62:801–815. 2015. View Article : Google Scholar : PubMed/NCBI
20	Das S, Kumar M, Negi V, Pattnaik B, Prakash YS, Agrawal A and Ghosh B: MicroRNA-326 regulates profibrotic functions of transforming growth factor-β in pulmonary fibrosis. Am J Respir Cell Mol Biol. 50:882–892. 2014. View Article : Google Scholar : PubMed/NCBI
21	Nagpal V, Rai R, Place AT, Murphy SB, Verma SK, Ghosh AK and Vaughan DE: miR-125b Is Critical for Fibroblast-to-Myofibroblast Transition and Cardiac Fibrosis. Circulation. 133:291–301. 2016. View Article : Google Scholar : PubMed/NCBI
22	Song L, Liu D, Zhao Y, He J, Kang H, Dai Z, Wang X, Zhang S and Zan Y: Sinomenine inhibits breast cancer cell invasion and migration by suppressing NF-κB activation mediated by IL-4/miR-324-5p/CUEDC2 axis. Biochem Biophys Res Commun. 464:705–710. 2015. View Article : Google Scholar : PubMed/NCBI
23	Bustin SA, Benes V, Garson JA, Hellemans J, Huggett J, Kubista M, Mueller R, Nolan T, Pfaffl MW, Shipley GL, et al: The MIQE guidelines: Minimum information for publication of quantitative real-time PCR experiments. Clin Chem. 55:611–622. 2009. View Article : Google Scholar : PubMed/NCBI
24	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) Method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
25	Butler J, Chirovsky D, Phatak H, McNeill A and Cody R: Renal function, health outcomes, and resource utilization in acute heart failure: A systematic review. Circ Heart Fail. 3:726–745. 2010. View Article : Google Scholar : PubMed/NCBI
26	Thiemermann C, Patel NS, Kvale EO, Cockerill GW, Brown PA, Stewart KN, Cuzzocrea S, Britti D, Mota-Filipe H and Chatterjee PK: High density lipoprotein (HDL) reduces renal ischemia/reperfusion injury. J Am Soc Nephrol. 14:1833–1843. 2003. View Article : Google Scholar : PubMed/NCBI
27	Zhong X, Chung AC, Chen HY, Meng XM and Lan HY: Smad3-mediated upregulation of miR-21 promotes renal fibrosis. J Am Soc Nephrol. 22:1668–1681. 2011. View Article : Google Scholar : PubMed/NCBI
28	Qin W, Chung AC, Huang XR, Meng XM, Hui DS, Yu CM, Sung JJ and Lan HY: TGF-β/Smad3 signaling promotes renal fibrosis by inhibiting miR-29. J Am Soc Nephrol. 22:1462–1474. 2011. View Article : Google Scholar : PubMed/NCBI
29	Chung AC, Huang XR, Meng X and Lan HY: miR-192 mediates TGF-beta/Smad3-driven renal fibrosis. J Am Soc Nephrol. 21:1317–1325. 2010. View Article : Google Scholar : PubMed/NCBI
30	Hyun J, Wang S, Kim J, Kim GJ and Jung Y: MicroRNA125b-mediated Hedgehog signaling influences liver regeneration by chorionic plate-derived mesenchymal stem cells. Sci Rep. 5:141352015. View Article : Google Scholar : PubMed/NCBI