Involvement of ERK pathway in albumin-induced MCP-1 expression in mouse proximal tubular cells

Am J Physiol Renal Physiol. 2003 May;284(5):F1037-45. doi: 10.1152/ajprenal.00230.2002. Epub 2003 Jan 7.


Persistent proteinuria has been indicated to be a major risk factor for the development of tubulointerstitial damage through a process of proinflammatory molecule expression. Monocyte chemoattractant protein-1 (MCP-1) was shown to contribute to recruitment of immune cells into the renal interstitium in acute and chronic renal diseases. However, the molecular mechanisms by which proteinuria causes MCP-1 expression in proximal tubular cells have not been fully clarified. In this study, we examined whether albumin overload-induced MCP-1 expression was regulated by mitogen-activated protein kinase (MAPK) in mouse proximal tubular (mProx) cells. Exposure of mProx cells to delipidated bovine serum albumin (BSA) induced mRNA and protein expression of MCP-1 in a time- and dose-dependent manner. BSA activated extracellular signal-regulated kinase (ERK1/2) and p38 MAPK. The MEK inhibitor U-0126 partially suppressed BSA-induced MCP-1 expression and MCP-1 promoter/luciferase reporter activity. U-0126 also inhibited an increase in nuclear factor-kappaB and activator protein-1 DNA-binding activity of MCP-1 promoter by protein overload in mProx cells. In addition, we found that U-0126 inhibited BSA-induced nuclear factor-kappaB reporter activity and inhibitory protein degradation in mProx cells. In conclusion, these findings indicate that ERK signaling is involved in BSA-induced MCP-1 expression in mProx cells.

MeSH terms

  • Animals
  • Cell Transformation, Viral
  • Cells, Cultured
  • Chemokine CCL2 / genetics
  • Chemokine CCL2 / metabolism*
  • DNA / metabolism
  • Enzyme Activation / physiology
  • I-kappa B Proteins / metabolism
  • Kidney Tubules, Proximal / cytology
  • Kidney Tubules, Proximal / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mitogen-Activated Protein Kinases / drug effects
  • Mitogen-Activated Protein Kinases / physiology*
  • NF-kappa B / physiology
  • Protein Isoforms / metabolism
  • RNA, Messenger / metabolism
  • Serum Albumin, Bovine / pharmacology*
  • Transcription Factor AP-1 / metabolism


  • Chemokine CCL2
  • I-kappa B Proteins
  • NF-kappa B
  • Protein Isoforms
  • RNA, Messenger
  • Transcription Factor AP-1
  • Serum Albumin, Bovine
  • DNA
  • Mitogen-Activated Protein Kinases