Involvement of ERK pathway in albumin-induced MCP-1 expression in mouse proximal tubular cells.
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.
Takaya
Kiho
K
Department of Medicine, Shiga University of Medical Science, Shiga 520-2192, Japan.
Koya
Daisuke
D
Isono
Motohide
M
Sugimoto
Toshiro
T
Sugaya
Takeshi
T
Kashiwagi
Atsunori
A
Haneda
Masakazu
M
D000818:Animals; D002472:Cell Transformation, Viral; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D004789:Enzyme Activation / Q000502:physiology; D020672:I-kappa B Proteins / Q000378:metabolism; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D020928:Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000502:physiology*; D016328:NF-kappa B / Q000502:physiology; D020033:Protein Isoforms / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012710:Serum Albumin, Bovine / Q000494:pharmacology*; D018808:Transcription Factor AP-1 / Q000378:metabolism
D018932:Chemokine CCL2; D020672:I-kappa B Proteins; D016328:NF-kappa B; D020033:Protein Isoforms; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; D012710:Serum Albumin, Bovine; D004247:DNA; D020928:Mitogen-Activated Protein Kinases