MiR-30a Inhibits the Epithelial--Mesenchymal Transition of Podocytes through Downregulation of NFATc3

Rui Peng; Li Zhou; Yuru Zhou; Ya Zhao; Qianyin Li; Dongsheng Ni; Yanxia Hu; Yaoshui Long; Jianing Liu; Zhongshi Lyu; Zhaomin Mao; Yue Yuan; Liyuan Huang; Hui Zhao; Ge Li; Qin Zhou

doi:10.3390/ijms161024032

MiR-30a Inhibits the Epithelial--Mesenchymal Transition of Podocytes through Downregulation of NFATc3

Int J Mol Sci. 2015 Oct 12;16(10):24032-47. doi: 10.3390/ijms161024032.

Authors

Rui Peng¹, Li Zhou², Yuru Zhou^{3

4}, Ya Zhao⁵, Qianyin Li⁶, Dongsheng Ni^{7

8}, Yanxia Hu^{9

10}, Yaoshui Long^{11

12}, Jianing Liu^{13

14}, Zhongshi Lyu¹⁵, Zhaomin Mao¹⁶, Yue Yuan¹⁷, Liyuan Huang¹⁸, Hui Zhao¹⁹, Ge Li²⁰, Qin Zhou²¹

Affiliations

¹ The Divsion of Molecular Nephrology and the Creative Training Center for Undergraduates, the M.O.E. Key Laboratory of Laboratory Medical Diagnostics, the College of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China. pengrui911@foxmail.com.
² The Divsion of Molecular Nephrology and the Creative Training Center for Undergraduates, the M.O.E. Key Laboratory of Laboratory Medical Diagnostics, the College of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China. shmily900519@foxmail.com.
³ The Divsion of Molecular Nephrology and the Creative Training Center for Undergraduates, the M.O.E. Key Laboratory of Laboratory Medical Diagnostics, the College of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China. zhouyuru93@sina.com.
⁴ The College of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China. zhouyuru93@sina.com.
⁵ The First Hospital of Xi'an, Xi'an 710002, China. zhaoya2508@sina.com.
⁶ The Divsion of Molecular Nephrology and the Creative Training Center for Undergraduates, the M.O.E. Key Laboratory of Laboratory Medical Diagnostics, the College of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China. lqianyin@gmail.com.
⁷ The Divsion of Molecular Nephrology and the Creative Training Center for Undergraduates, the M.O.E. Key Laboratory of Laboratory Medical Diagnostics, the College of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China. dongshengni@outlook.com.
⁸ The College of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China. dongshengni@outlook.com.
⁹ The Divsion of Molecular Nephrology and the Creative Training Center for Undergraduates, the M.O.E. Key Laboratory of Laboratory Medical Diagnostics, the College of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China. hyx_zuichu@outlook.com.
¹⁰ The College of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China. hyx_zuichu@outlook.com.
¹¹ The Divsion of Molecular Nephrology and the Creative Training Center for Undergraduates, the M.O.E. Key Laboratory of Laboratory Medical Diagnostics, the College of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China. lys960110@sina.com.
¹² The College of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China. lys960110@sina.com.
¹³ The Divsion of Molecular Nephrology and the Creative Training Center for Undergraduates, the M.O.E. Key Laboratory of Laboratory Medical Diagnostics, the College of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China. keithljn@sina.cn.
¹⁴ The College of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China. keithljn@sina.cn.
¹⁵ The Divsion of Molecular Nephrology and the Creative Training Center for Undergraduates, the M.O.E. Key Laboratory of Laboratory Medical Diagnostics, the College of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China. zhongshilyu@sina.com.
¹⁶ The Divsion of Molecular Nephrology and the Creative Training Center for Undergraduates, the M.O.E. Key Laboratory of Laboratory Medical Diagnostics, the College of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China. zhaominmao@sina.com.
¹⁷ The Divsion of Molecular Nephrology and the Creative Training Center for Undergraduates, the M.O.E. Key Laboratory of Laboratory Medical Diagnostics, the College of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China. yyokyy1126@hotmail.com.
¹⁸ The Divsion of Molecular Nephrology and the Creative Training Center for Undergraduates, the M.O.E. Key Laboratory of Laboratory Medical Diagnostics, the College of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China. lyhuang0603@sina.com.
¹⁹ Key Laboratory for Regenerative Medicine, Ministry of Education, School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China. zhaohui@cuhk.edu.hk.
²⁰ Core Facility of Experiments Training, Chongqing Medical University, Chongqing 400016, China. geli@cqmu.edu.cn.
²¹ The Divsion of Molecular Nephrology and the Creative Training Center for Undergraduates, the M.O.E. Key Laboratory of Laboratory Medical Diagnostics, the College of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China. zhouqin@cqmu.edu.cn.

Abstract

MicroRNAs (miRNAs) possess an important regulating effect among numerous renal diseases, while their functions in the process of epithelial-to-mesenchymal transition (EMT) after podocyte injury remain unclear. The purpose of our study is to identify the potential functions of miR-30a in EMT of podocytes and explore the underlying mechanisms of miR-30a in the impaired podocytes. The results revealed that downregulation of miR-30a in podocyte injury animal models and patients, highly induced the mesenchymal markers of EMT including Collagen I, Fibronectin and Snail. Furthermore, overexpression of miR-30a enhances epithelial markers (E-cadherin) but diminished mesenchymal markers (Collagen I, Fibronectin and Snail) in podocytes. In addition, we established miR-30a target NFATc3, an important transcription factor of Non-canonical Wnt signaling pathway. More importantly, our findings demonstrated that the augmentation of miR-30a level in podocytes inhibits the nuclear translocation of NFATc3 to protect cytoskeleton disorder or rearrangement. In summary, we uncovered the protective function of miR30a targeting NFATc3 in the regulation of podocyte injury response to EMT.

Keywords: epithelial-to-mesenchymal transition (EMT); microRNA-30a (miR-30a); nuclear factor of activated T cells 3 (NFATc3); podocyte.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Active Transport, Cell Nucleus / genetics
Animals
Cadherins / biosynthesis
Cell Line
Collagen Type I / biosynthesis
Down-Regulation
Epithelial-Mesenchymal Transition / genetics
Epithelial-Mesenchymal Transition / physiology*
Fibronectins / biosynthesis
Gene Expression Regulation, Neoplastic
Glomerulosclerosis, Focal Segmental / pathology
HEK293 Cells
Humans
Mice
Mice, Inbred BALB C
MicroRNAs / biosynthesis*
MicroRNAs / genetics
NFATC Transcription Factors / biosynthesis*
NFATC Transcription Factors / metabolism
Podocytes / metabolism*
Snail Family Transcription Factors
Transcription Factors / biosynthesis
Wnt Signaling Pathway / physiology

Substances

Cadherins
Collagen Type I
Fibronectins
MIRN30b microRNA, human
MicroRNAs
NFATC Transcription Factors
NFATC3 protein, human
Snail Family Transcription Factors
Transcription Factors