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Effect of miR-21 on Renal Fibrosis by Regulating MMP-9 and TIMP1 in kk-ay Diabetic Nephropathy Mice

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Abstract

MicroRNAs (miRs) play important roles in initiation and progression of many pathologic processes. However, the roles of miRs in diabetic nephropathy remain unclear. This study was to determine whether miR-21 was involved in diabetic nephropathy and to explore the relationship between miR-21 and MMP9/TIMP1 expression in diabetic nephropathy. In situ hybridization studies showed that miR-21 was primarily localized and distributed in cortical glomerular and renal tubular cells in diabetic kk-ay kidney. Real-time quantitative RT-PCR demonstrated that the expression of miR-21 was significantly increased in kk-ay mice, compared with control C57BL mice. Interestingly, miR-21 expression positively correlated with urine albumin creatine ratio (ACR), TIMP1, collagen IV (ColIV), and fibronectin (FN); while negatively correlated with creatine clearance ratio (Ccr) and MMP-9 protein. Importantly, antagomir-21 not only ameliorated Ccr and ACR but also decreased TIMP1, ColIV, and FN proteins. In conclusion, our data demonstrate that miR-21 contributes to renal fibrosis by mediating MMP9/TIMP1 and that inhibition of miR-21 may be a novel target for diabetic nephropathy.

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Acknowledgments

This study was supported by Grants from the Major National Basic Research Program of China (973 Program, No. 2012CB518602), the National Natural Science Foundation of China (No. 81173238), and Scientific Research Project of Beijing Educational Committee (No. KZ201110025025).

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Authors and Affiliations

  1. School of Traditional Chinese Medicine, Capital Medical University, Beijing, People’s Republic of China

    Jinyang Wang, Yanbin Gao, Dawei Zou, Zhiyao Zhu & Xuan Zhao

  2. Department of Endocrinology, Beijing Tongren Hospital, Capital Medical University, Beijing, People’s Republic of China

    Jinyang Wang & Jinkui Yang

  3. Department of Endocrinology and Metabolism, Capital Medical University, Beijing, People’s Republic of China

    Jinyang Wang

  4. Department of Endocrine, Beijing University of Chinese Medicine, Beijing, People’s Republic of China

    Mingfei Ma & Minzhou Li

  5. Chinese Medical College, Capital Medical University, #10, Youanmenwai Xitoutiao, Fengtai District, Beijing, 100069, People’s Republic of China

    Yanbin Gao

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  1. Jinyang Wang
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Correspondence to Yanbin Gao.

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Wang, J., Gao, Y., Ma, M. et al. Effect of miR-21 on Renal Fibrosis by Regulating MMP-9 and TIMP1 in kk-ay Diabetic Nephropathy Mice. Cell Biochem Biophys 67, 537–546 (2013). https://doi.org/10.1007/s12013-013-9539-2

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