LncRNA-NR_033515 promotes proliferation, fibrogenesis and epithelial-to-mesenchymal transition by targeting miR-743b-5p in diabetic nephropathy

Biomed Pharmacother. 2018 Oct:106:543-552. doi: 10.1016/j.biopha.2018.06.104. Epub 2018 Jul 11.

Abstract

Diabetic nephropathy (DN) is a crucial microvascular complication of diabetes. Long non-coding RNAs (lncRNAs) participate in the occurrence and development of various diseases, but the function and regular mechanism of lncRNA-NR_033515 in DN is still unclear. In the present study, we demonstrated that the expression of NR_033515 was significantly increased in the serum of DN patients and was related to the different stages of DN. NR_033515 was also positively associated with diagnostic markers of DN (KIM-1 and NGAL). Overexpression of NR_033515 promoted proliferation, and inhibited apoptosis of MMC cells and increased the expression levels of proliferation-related genes. NR_033515 also accelerated the expression levels of fibrogenesis-related genes. TGF-β1 enhanced NR_033515-induced Epithelial-mesenchymal transition (EMT), while NR_033515 over-expression accelerated TGF-β1-induced EMT. Furthermore, we found that NR_033515 promoted cell proliferation and regulated P38, ASK1, Fibronectin, α-SMA, E-cadherin, and Vimentin expressions by miR-743b-5p. Therefore, our data indicated the potential role of NR_033515 in the proliferation, fibrogenesis and EMT in DN. NR_033515 could be a pivotal potential diagnostic and therapeutic target for the treatment of DN.

Keywords: Diabetic nephropathy; Epithelial-to-mesenchymal transition; Fibrogenesis; NR_033515; Proliferation; miR-743b-5p.

MeSH terms

  • Animals
  • Apoptosis
  • Case-Control Studies
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Cell Proliferation*
  • Diabetic Nephropathies / blood
  • Diabetic Nephropathies / genetics
  • Diabetic Nephropathies / metabolism*
  • Diabetic Nephropathies / pathology
  • Epithelial-Mesenchymal Transition* / genetics
  • Fibrosis
  • Gene Expression Regulation
  • Genetic Markers
  • HEK293 Cells
  • Humans
  • Mesangial Cells / metabolism*
  • Mesangial Cells / pathology
  • Mice
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • RNA, Long Noncoding / blood
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Signal Transduction
  • Time Factors

Substances

  • Cell Cycle Proteins
  • Genetic Markers
  • MicroRNAs
  • Mirn743 microRNA, human
  • Mirn743 microRNA, mouse
  • RNA, Long Noncoding