Homocysteine stimulates monocyte chemoattractant protein-1 expression in mesangial cells via NF-κB activation.
Cheung, G.T.Y., Siow, Y.L., and O, K. (2008). "Homocysteine stimulates monocyte chemoattractant protein-1 expression in mesangial cells via NF-κB activation.", Canadian Journal of Physiology and Pharmacology, 86(3), pp. 88-96. doi : 10.1139/Y08-002
Hyperhomocysteinemia is regarded as an independent risk factor for cardiovascular disorders. Although renal dysfunction or failure is one of the important factors causing hyperhomocysteinemia, the role of homocysteine (Hcy) in the development of glomerulosclerosis is largely unknown. One of the key events in the pathogenesis of glomerulosclerosis is the infiltration of circulating monocytes into affected glomeruli. The objective of the present study was to investigate the effect of Hcy on the expression of monocyte chemoattractant protein-1 (MCP-1) in kidney mesangial cells and the mechanisms involved. Levels of MCP-1 and mRNA were significantly elevated in Hcy-treated rat mesangial cells. This increase was associated with activation of NF-κB as a result of increased phosphorylation of the inhibitor protein IκBα. Monocyte chemotactic activity in these cells was also enhanced. In addition, there was a significant elevation of superoxide anion produced by Hcy-treated cells, which preceded the increased phosphorylation of IκBα. Addition of superoxide dismutase or NF-κB inhibitors to the culture medium abolished Hcy-induced NF-κB activation and MCP-1 expression. Taken together, these results indicate that Hcy induced MCP-1 expression in mesangial cells. Such a process was mediated by oxidative stress and NF-κB activation. This may further aggravate renal function in patients with hyperhomocysteinemia.