Glomerular mesangial cells (MCs) hypertrophy is one of the earliest pathological abnormalities in diabetic nephropathy (DN), which correlates with eventual glomerulosclerosis.
A recent study led by researchers from Shanghai Jiao Tong University School of Medicine aimed to investigate the therapeutic role of miRNA in diabetic glomerular MCs hypertrophy and synthesis of extracellular matrix (ECM). MiRNA microarray analysis revealed a significant up-regulation of miR-214 in the renal cortex of diabetic db/db mice, which was confirmed by real-time PCR of isolated glomeruli and primary cultured human MCs. In vitro studies showed that inhibition of miR-214 significantly reduced expression of α-SMA, SM22 and collagen IV, and partially restored phosphatase and tensin homolog (PTEN) protein level in high glucose-stimulated human MCs. Furthermore, they identified PTEN as the target of miR-214 by a luciferase assay in HEK293 cells. Moreover, overexpression of PTEN ameliorated miR-214-mediated diabetic MC hypertrophy while knockdown of PTEN mimicked the MC hypertrophy. In vivo study further confirmed that inhibition of miR-214 significantly decreased the expression of SM22, α-SMA and collagen IV, partially restored PTEN level, and attenuated albuminuria and mesangial expansion in db/db mice.
In conclusion, cross talk between miR-214 and PTEN attenuated glomerular hypertrophy under diabetic conditions in vivo and in vitro. Therefore, miR-214 may represent a novel therapeutic target for DN.
Bioinformatics analysis of differential miRNAs
(A) GO analysis of target genes for down-regulation of miRNAs. (B) GO analysis of target genes for up-regulation of miRNAs. (C) Prediction of miRNA-target gene-network (green circles represent target genes, yellow boxes represent down-regulation of miRNAs and red boxes represent up-regulation of miRNAs, respectively).
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Reference
X. Wang, E. Shen, Y. Wang, J. Li, D. Cheng, Y. Chen, D. Gui, N. Wang (2016) Cross talk between miR-214 and PTEN attenuates glomerular hypertrophy under diabetic conditions Sci. Rep. 6:31506 doi: 10.1038/srep31506 [article]