Molecular Therapy: Nucleic Acids (Sep 2019)

lncRNA NR_038323 Suppresses Renal Fibrosis in Diabetic Nephropathy by Targeting the miR-324-3p/DUSP1 Axis

  • Yanni Ge,
  • Juan Wang,
  • Dengke Wu,
  • Yu Zhou,
  • Shuangfa Qiu,
  • Junxiang Chen,
  • Xuejin Zhu,
  • Xudong Xiang,
  • Huiling Li,
  • Dongshan Zhang

Journal volume & issue
Vol. 17
pp. 741 – 753

Abstract

Read online

Several studies have suggested that long intergenic noncoding RNAs are involved in the progression of diabetic nephropathy (DN). However, the exact role and regulatory mechanism of long noncoding RNA (lncRNA) NR_038323 in diabetic nephropathy (DN) remain largely unclear. In the present study, we found that lncRNA NR_038323 overexpression ameliorated the high glucose (HG)-induced expression levels of collagen I, collagen IV, and fibronectin, whereas lncRNA NR_038323 knockdown exerted the opposite effects. Moreover, the results of bioinformatic prediction, luciferase assay, and fluorescence in situ hybridization (FISH) demonstrated that lncRNA NR_038323 directly interacted with miR-324-3p. Additionally, miR-324-3p mimic aggravated the HG-induced expression levels of collagen I, collagen IV, and fibronectin by dual-specificity protein phosphatase-1 (DUSP1) expression to activate p38 mitogen-activated protein kinase (MAPK) and ERK1/2 pathways. In contrast, overexpression of DUSP1 attenuated the HG-induced expression levels of collagen I, collagen IV, and fibronectin via inactivation of p38 MAPK and ERK1/2 pathways. In addition, lncRNA NR_038323 knockdown increased the expression levels of collagen I, collagen IV, and fibronectin by upregulating DUSP1 expression during HG treatment, which were markedly reversed by miR-324-3p inhibitor. Furthermore, these molecular changes were verified in the human kidney samples of DN patients. Finally, overexpression of lncRNA NR_038323 ameliorated the interstitial fibrosis in STZ-induced diabetic nephrology (DN) rat via miR-324-3p/DUSP1/p38MAPK and ERK1/2 axis. In conclusion, our data indicate that overexpression of lncRNA NR_038323 may suppress HG-induced renal fibrosis via the miR-324-3p/DUSP1/p38MAPK and ERK1/2 axis, which provides new insights into the pathogenesis of DN. Keywords: diabetic nephropathy, lncRNA NR_038323, miR-324-3p, DUSP1