Endocrine Abstracts (2009) 20 P679

Retinol-binding protein 4 activates TGB-[beta]1 expression and apoptosis via phosphorylation of JNK and MAPK in HEK cells

Shyi-Jang Shin & Chao-Hung Chen

Kaohsiung Medical University, Kaohsiung, Taiwan.

Serum retinol-binding protein 4 (RBP4), a new adipocytokine, was reported to increase insulin resistance. RBP4 was significantly elevated in type 2 diabetic patients with microalbuminuria and macroalbuminuria as compared with normoalbuminuric patients. Some adipocytokines have been found to induce cell injury. Therefore, we investigated whether RBP4 could modulate JNK, p38MAPK, ERK and TGF-β1 expression in HEK293 cells by using transfection of p38MAPK and JNK small interfering RNA (siRNA). HEK cells were grown without transfection or with transfection with p38MAPK and JNK small interfering RNA (siRNA) plasmid. Cells were also transfected with control siRNA. HEK cells were stimulated with RBP4 (0, 2.5, 12.5, 25 and 59 μg/dl) to modulate the expression of TGF-β1 and phosphorylation of JNK, ERK and p38MAPK. Our results showed that the addition of RBP4 significantly increased phosphorylation of JNK, p38MAPK and ERK, and TGF-β1 expression in a dose-dependent pattern in untransfected cells. The transfection of p38MAPK and JNK siRNA significantly decreased the expression of p38MAPK and JNK, but also markedly attenuated RBP4-activated expression of TGF-β1. Additionally, the transfection of p38MAPK and JNK siRNA attenuated RBP4-activated caspase expression and DNA fragmentation in HEK cells. In conclusion, our results demonstrated that RBP4 can increase TGF-β1 expression and induce apoptosis through the activation of JNK, p38MAPK and ERK phosphorylation in HEK293 cells.

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