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Updated: Jul 10, 2026
Quantification of Monocyte Chemotactic Activity In Vivo and Characterization of Blood Monocyte Derived Macrophages
Published on: August 12, 2019
Homocysteine stimulates monocyte chemoattractant protein-1 expression in the kidney via nuclear factor-kappaB
Sun-Young Hwang1, Connie W H Woo, Kathy K W Au-Yeung
1Department of Animal Science, University of Manitoba, Winnipeg, Canada.
Insights
High homocysteine (Hcy) levels, or hyperhomocysteinemia, increase kidney inflammation by activating NF-kappaB, leading to elevated MCP-1 expression. This inflammatory response may contribute to chronic kidney disease development.
Area of Science:
- Nephrology
- Cardiovascular Medicine
- Molecular Biology
Background:
- Hyperhomocysteinemia (elevated blood homocysteine levels) is linked to cardiovascular issues and kidney dysfunction.
- The direct impact of homocysteine on kidney damage and the underlying mechanisms remain unclear.
- Inflammation, specifically chemokine expression like MCP-1, is implicated in renal disease progression.
Purpose of the Study:
- To investigate the effect of hyperhomocysteinemia on kidney Monocyte Chemoattractant Protein-1 (MCP-1) expression.
- To elucidate the molecular mechanism, particularly the role of Nuclear Factor-kappaB (NF-kappaB), in hyperhomocysteinemia-induced renal inflammation.
- To examine these effects in both a rat model and human kidney proximal tubular cells.
Main Methods:
- Induced hyperhomocysteinemia in rats using a high-methionine diet for 12 weeks.
- Measured MCP-1 mRNA and protein levels, and NF-kappaB activity in rat kidneys.
- Utilized NF-kappaB inhibitors in rats and transfected human kidney tubular cells with decoy NF-kappaB oligodeoxynucleotides to assess the role of NF-kappaB.
Main Results:
- Hyperhomocysteinemia significantly increased MCP-1 mRNA and protein levels in rat kidneys.
- Elevated NF-kappaB activity was observed in the kidneys of hyperhomocysteinemic rats.
- Inhibition of NF-kappaB activation prevented hyperhomocysteinemia-induced MCP-1 expression in both rat kidneys and human tubular cells.
Conclusions:
- Hyperhomocysteinemia stimulates MCP-1 expression in the kidney through NF-kappaB activation.
- This NF-kappaB-mediated inflammatory response may play a significant role in renal injury associated with elevated homocysteine levels.
- The findings highlight a potential molecular pathway linking hyperhomocysteinemia to chronic kidney disease.
Abstract:
Hyperhomocysteinemia, or an elevation of blood homocysteine (Hcy) levels, is associated with cardiovascular disorders. Although kidney dysfunction is an important risk factor causing hyperhomocysteinemia, the direct effect of Hcy on the kidney is not well documented. There is a positive association between an elevation of blood Hcy levels and the development of chronic kidney disease. Inflammatory response such as increased chemokine expression has been implicated as one of the mechanisms for renal disease. Monocyte chemoattractant protein-1 (MCP-1) is a potent chemokine that is involved in the inflammatory response in renal disease. Nuclear factor-kappaB (NF-kappaB) plays an important role in upregulation of MCP-1 expression. We investigated the effect of hyperhomocysteinemia on MCP-1 expression and the molecular mechanism underlining such an effect in rat kidneys as well as in proximal tubular cells. Hyperhomocysteinemia was induced in rats fed a high-methionine diet for 12 wk. The MCP-1 mRNA expression and MCP-1 protein levels were significantly increased in kidneys isolated from hyperhomocysteinemic rats. The NF-kappaB activity was significantly increased in the same kidneys. Pretreatment of hyperhomocysteinemic rats with a NF-kappaB inhibitor abolished hyperhomocysteinemia-induced MCP-1 expression in the kidney. To confirm the causative role of NF-kappaB activation in MCP-1 expression, human kidney proximal tubular cells were transfected with decoy NF-kappaB oligodeoxynucleotide to inhibit NF-kappaB activation. Such a treatment prevented Hcy-induced MCP-1 mRNA expression in tubular cells. Our results suggest that hyperhomocysteinemia stimulates MCP-1 expression in the kidney via NF-kappaB activation. Such an inflammatory response may contribute to renal injury associated with hyperhomocysteinemia.
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