Emodin suppresses hyperglycemia-induced proliferation and fibronectin expression in mesangial cells via inhibiting cFLIP

PLoS One. 2014 Apr 1;9(4):e93588. doi: 10.1371/journal.pone.0093588. eCollection 2014.

Abstract

As one of the most serious microvascular complications of diabetes and a major cause of end stage renal disease, diabetic nephropathy (DN) is calling for effective treatment strategies. Here, we provide evidence that hyperglycemia can induce proliferation and decreasing apoptosis of mesangial cells (MCs) and subsequent renal dysfunction by up-regulating cellular FLICE-inhibitory protein (cFLIP). Treatment with emodin significantly turns down the accelerated cell cycle and proliferation of MCs cultured in high glucose (HG) via inhibiting cFLIP. In vitro, knockdown of cFLIP can arrest cell cycle and accelerate cell death by activating caspase-8, caspase-3 and caspase-9, and down-regulate proliferating cell nuclear antigen (PCNA). Our results also suggest that emodin regulates cFLIP expression in transcriptional level. Importantly, emodin lessens proteinuria and fibronectin expression in early-stage of streptozotocin (STZ)-induced diabetic rats. These findings demonstrate that emodin represent a promising strategy to prevent renal dysfunction in early-stage of diabetes mellitus.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • CASP8 and FADD-Like Apoptosis Regulating Protein / antagonists & inhibitors
  • CASP8 and FADD-Like Apoptosis Regulating Protein / biosynthesis*
  • Cell Cycle Checkpoints / drug effects
  • Cell Proliferation / drug effects
  • Diabetes Mellitus, Experimental / drug therapy
  • Diabetes Mellitus, Experimental / genetics
  • Diabetes Mellitus, Experimental / pathology
  • Diabetic Nephropathies / drug therapy*
  • Diabetic Nephropathies / etiology
  • Diabetic Nephropathies / genetics
  • Emodin / administration & dosage*
  • Fibronectins / biosynthesis*
  • Fibronectins / genetics
  • Gene Expression Regulation / drug effects
  • Gene Knockdown Techniques
  • Humans
  • Hyperglycemia / complications
  • Hyperglycemia / pathology
  • Mesangial Cells / metabolism
  • Mesangial Cells / pathology
  • Rats
  • Renal Insufficiency / drug therapy*
  • Renal Insufficiency / genetics
  • Renal Insufficiency / pathology

Substances

  • CASP8 and FADD-Like Apoptosis Regulating Protein
  • Fibronectins
  • Emodin

Grants and funding

The authors have no support or funding to report.