Effect of PKC-β Signaling Pathway on Expression of MCP-1 and VCAM-1 in Different Cell Models in Response to Advanced Glycation End Products (AGEs)

Toxins

Lisienny C. T. Rempel¹  Alessandra B. Finco¹  Rayana A. P. Maciel¹  Bruna Bosquetti¹  Larissa M. Alvarenga¹  Wesley M. Souza³  Roberto Pecoits-Filho²  Andrບ E. M. Stinghen¹ 

[1] Experimental Nephrology Laboratory, Basic Pathology Department, Universidade Federal do Paraná; Av. Cel. Francisco H. dos Santos, S/N, Jd. das Américas, Curitiba, PR, 81.531-980, Brazil; E-Mails:;School of Medicine, Pontifícia Universidade Católica do Paraná, Av. Imaculada Conceição, 1155, Curitiba, PR, 80.215-901, Brazil; E-Mail:;Universidade Tuiuti do Paraná, Rua Sydnei Antonio Rangel Santos, 238, Santo Inácio, Curitiba, PR, 82.010-330, Brazil; E-Mail:

关键词: AGEs;    chronic kidney disease;    endothelial dysfunction;    PKC-β pathway;    MCP-1;    VCAM-1;   

DOI  :  10.3390/toxins7051722

来源: mdpi

【 摘 要 】

Advanced glycation end products (AGEs) are compounds classified as uremic toxins in patients with chronic kidney disease that have several pro-inflammatory effects and are implicated in the development of cardiovascular diseases. To explore the mechanisms of AGEs–endothelium interactions through the receptor for AGEs (RAGE) in the PKC-β pathway, we evaluated the production of MCP-1 and VCAM-1 in human endothelial cells (HUVECs), monocytes, and a coculture of both. AGEs were prepared by albumin glycation and characterized by absorbance and electrophoresis. The effect of AGEs on cell viability was assessed with an MTT assay. The cells were also treated with AGEs with and without a PKC-β inhibitor. MCP-1 and VCAM-1 in the cell supernatants were estimated by ELISA, and RAGE was evaluated by immunocytochemistry. AGEs exposure did not affect cell viability, but AGEs induced RAGE, MCP-1, and VCAM-1 expression in HUVECs. When HUVECs or monocytes were incubated with AGEs and a PKC-β inhibitor, MCP-1 and VCAM-1 expression significantly decreased. However, in the coculture, exposure to AGEs and a PKC-β inhibitor produced no significant effect. This study demonstrates, in vitro, the regulatory mechanisms involved in MCP-1 production in three cellular models and VCAM-1 production in HUVECs, and thus mimics the endothelial dysfunction caused by AGEs in early atherosclerosis. Such mechanisms could serve as therapeutic targets to reduce the harmful effects of AGEs in patients with chronic kidney disease.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.