Research Papers:

MicroRNA-27a promotes renal tubulointerstitial fibrosis via suppressing PPARγ pathway in diabetic nephropathy

Xiaoyan Hou, Jianwei Tian, Jian Geng, Xiao Li, Xun Tang, Jun Zhang and Xiaoyan Bai _

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Oncotarget. 2016; 7:47760-47776. https://doi.org/10.18632/oncotarget.10283

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Xiaoyan Hou1,2,3, Jianwei Tian1, Jian Geng4, Xiao Li5, Xun Tang2, Jun Zhang2, Xiaoyan Bai1

1Division of Nephrology, Nanfang Hospital, Southern Medical University, National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Guangdong Provincial Institute of Nephrology, Guangzhou, Guangdong, PR China

2Department of Nephrology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, PR China

3Department of Nephrology, The First Affiliated Hospital, Inner Mongolia Medical University, Hohhot, Inner Mongolia, PR China

4Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, PR China

5Department of Emergency, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, PR China

Correspondence to:

Xiaoyan Bai, email: [email protected], [email protected]

Jun Zhang, email: [email protected]

Keywords: miR-27a, PPARγ, TGF-β/Smad3, renal tubulointerstitial fibrosis, diabetic nephropathy

Received: January 27, 2016     Accepted: June 12, 2016     Published: June 24, 2016


MicroRNA-27a (miR-27a) upregulation has been identified in diabetes, but the pathogenesis of miR-27a in renal tubulointerstitial fibrosis (TIF) in diabetic nephropathy (DN) has not been elucidated. Herein, we found that high glucose stimulated miR-27a expression, which directly inhibited PPARγ and promoted fibrosis in NRK-52E cells. The functional relevance of miR-27a-dependent PPARγ decrease was proven by inhibition or overexpression of miR-27a both in vitro and in streptozotocin-induced diabetic rats. MiR-27a, via repression of PPARγ, activates the TGF-β/Smad3 signaling and contributes to the expressional changes of connective tissue growth factor (CTGF), Fibronectin and Collagen I, key mediators of fibrosis. Furthermore, we provide evidences that plasma miR-27a upregulation contributed to unfavorable renal function and increased TIF in renal tissues of diabetic rats and DN patients. Notably, miR-27a exhibited clinical and biological relevance as it was linked to elevated serum creatinine, proteinuria, urinary N-acetyl-β-D-glucosaminidase (NAG), and reduced estimated glomerular filtration rate (eGFR). Thus, we propose a novel role of the miR-27a-PPARγ axis in fostering the progression toward more deteriorated renal TIF in DN. Monitoring plasma miR-27a level and its association with PPARγ can be used to reflect the severity of renal TIF. Targeting miR-27a could be evaluated as a potential therapeutic approach for DN.

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