Differential expression and therapeutic efficacy of microRNA-346 in diabetic nephropathy mice

Zhang,Yong; Xiao,Hou‑Qin; Wang,Yang; Yang,Zhuo‑Shun; Dai,Long‑Jun; Xu,Yan‑Cheng

doi:10.3892/etm.2015.2468

July-2015 Volume 10 Issue 1

Full Size Image

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

An International Open Access Journal Devoted to General Medicine.

July-2015 Volume 10 Issue 1

Full Size Image

Article Open Access

Differential expression and therapeutic efficacy of microRNA-346 in diabetic nephropathy mice

Authors:
- Yong Zhang
- Hou‑Qin Xiao
- Yang Wang
- Zhuo‑Shun Yang
- Long‑Jun Dai
- Yan‑Cheng Xu
View Affiliations / Copyright

Affiliations: Department of Endocrinology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China, Department of Nephrology, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China, The Research Center for High Altitude Medicine, Medical College, Qinghai University, Xining, Qinghai 810001, P.R. China, Hubei Key Laboratory of Stem Cell Research, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China

Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
Pages: 106-112
|
Published online on: April 30, 2015

https://doi.org/10.3892/etm.2015.2468
Expand metrics +

Abstract

Diabetic nephropathy (DN) is a major cause of end‑stage renal disease, in which the SMAD signaling pathway plays an important role. The aim of the present study was to identify differentially expressed microRNAs (miRNAs) during the progression of DN and to investigate a selected miRNA in relation to SMAD3/4 and its therapeutic efficacy. The miRNA microarray was used to identify differentially expressed miRNAs in db/db DN mice. Reverse transcription‑quantitative polymerase chain reaction and immunoblot analyses were used to detect SMAD3/4 expression. The development of DN in the db/db mice was demonstrated by glucose dysregulation and typical morphological changes in the kidney. miRNA‑346 (miR‑346) was identified as one of the differentially expressed miRNAs. The expression of SMAD3/4 was significantly attenuated by miR‑346 administration and the therapeutic effects of miR‑346 were observed in the DN mouse models. miR‑346 was identified as a negative regulator of SMAD3/4. SMAD3/4 was upregulated in the renal tissue of db/db mice. The administration of miR‑346 attenuated the SMAD3/4 expression in renal tissue and ameliorated the renal function and glomerular histology in DN mice. This study paves the way for clinical studies of miR‑346 in DN.

View Figures

View References

1	Danaei G, Finucane MM, Lu Y, et al: Global Burden of Metabolic Risk Factors of Chronic Diseases Collaborating Group (Blood Glucose): National, regional, and global trends in fasting plasma glucose and diabetes prevalence since 1980: Systematic analysis of health examination surveys and epidemiological studies with 370 country-years and 2.7 million participants. Lancet. 378:31–40. 2011. View Article : Google Scholar : PubMed/NCBI
2	Gilbertson DT, Liu J, Xue JL, et al: Projecting the number of patients with end-stage renal disease in the United States to the year 2015. J Am Soc Nephrol. 16:3736–3741. 2005. View Article : Google Scholar : PubMed/NCBI
3	Hagiwara S, McClelland A and Kantharidis P: MicroRNA in diabetic nephropathy: Renin angiotensin, aGE/RAGE, and oxidative stress pathway. J Diabetes Res. 2013:1737832013. View Article : Google Scholar : PubMed/NCBI
4	Forbes JM and Cooper ME: Mechanisms of diabetic complications. Physiol Rev. 93:137–188. 2013. View Article : Google Scholar : PubMed/NCBI
5	Adler S: Diabetic nephropathy: Linking histology, cell biology, and genetics. Kidney Int. 66:2095–2106. 2004. View Article : Google Scholar : PubMed/NCBI
6	Susztak K, Raff AC, Schiffer M and Böttinger EP: Glucose-induced reactive oxygen species cause apoptosis of podocytes and podocyte depletion at the onset of diabetic nephropathy. Diabetes. 55:225–233. 2006. View Article : Google Scholar : PubMed/NCBI
7	Sharma K, McCue P and Dunn SR: Diabetic kidney disease in the db/db mouse. Am J Physiol Renal Physiol. 284:F1138–F1144. 2003. View Article : Google Scholar : PubMed/NCBI
8	Yates LA, Norbury CJ and Gilbert RJ: The long and short of microRNA. Cell. 153:516–519. 2013. View Article : Google Scholar : PubMed/NCBI
9	Soifer HS, Rossi JJ and Saetrom P: MicroRNAs in disease and potential therapeutic applications. Mol Ther. 15:2070–2079. 2007. View Article : Google Scholar : PubMed/NCBI
10	Fabian MR, Sonenberg N and Filipowicz W: Regulation of mRNA translation and stability by microRNAs. Annu Rev Biochem. 79:351–379. 2010. View Article : Google Scholar : PubMed/NCBI
11	Yang ZS, Tang XJ, Guo XR, et al: Cancer cell-oriented migration of mesenchymal stem cells engineered with an anticancer gene (PTEN): An imaging demonstration. Onco Targets Ther. 7:441–446. 2014.PubMed/NCBI
12	Krek A, Grün D, Poy MN, et al: Combinatorial microRNA target predictions. Nat Genet. 37:495–500. 2005. View Article : Google Scholar : PubMed/NCBI
13	Lorenzen JM, Haller H and Thum T: MicroRNAs as mediators and therapeutic targets in chronic kidney disease. Nat Rev Nephrol. 7:286–294. 2011. View Article : Google Scholar : PubMed/NCBI
14	Krupa A, Jenkins R, Luo DD, et al: Loss of MicroRNA-192 promotes fibrogenesis in diabetic nephropathy. J Am Soc Nephrol. 21:438–447. 2010. View Article : Google Scholar : PubMed/NCBI
15	Du B, Ma LM, Huang MB, Zhou H, Huang HL, Shao P, Chen YQ and Qu LH: High glucose down-regulates miR-29a to increase collagen IV production in HK-2 cells. FEBS Lett. 584:811–816. 2010. View Article : Google Scholar : PubMed/NCBI
16	Wang Q, Wang Y, Minto AW, et al: MicroRNA-377 is up-regulated and can lead to increased fibronectin production in diabetic nephropathy. FASEB J. 22:4126–4135. 2008. View Article : Google Scholar : PubMed/NCBI
17	Wang G, Kwan BC, Lai FM, et al: Intrarenal expression of miRNAs in patients with hypertensive nephrosclerosis. Am J Hypertens. 23:78–84. 2010. View Article : Google Scholar : PubMed/NCBI
18	Tay Y, Rinn J and Pandolfi PP: The multilayered complexity of ceRNA crosstalk and competition. Nature. 505:344–352. 2014. View Article : Google Scholar : PubMed/NCBI
19	Ling H, Fabbri M and Calin GA: MicroRNAs and other non-coding RNAs as targets for anticancer drug development. Nat Rev Drug Discov. 12:847–865. 2013. View Article : Google Scholar : PubMed/NCBI
20	Meng XM, Huang XR, Chung AC, et al: Smad2 protects against TGF-beta/Smad3-mediated renal fibrosis. J Am Soc Nephrol. 21:1477–1487. 2010. View Article : Google Scholar : PubMed/NCBI
21	Meng XM, Chung AC and Lan HY: Role of the TGF-β/BMP-7/Smad pathways in renal diseases. Clin Sci (Lond). 124:243–254. 2013. View Article : Google Scholar : PubMed/NCBI
22	Kantharidis P, Wang B, Carew RM and Lan HY: Diabetes complications: The microRNA perspective. Diabetes. 60:1832–1837. 2011. View Article : Google Scholar : PubMed/NCBI

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Differential expression and therapeutic efficacy of microRNA-346 in diabetic nephropathy mice

This article is mentioned in:

Abstract

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Related Articles