RhoA induces expression of inflammatory cytokine in adipocytes.
Rho GTPase regulates actin cytoskeleton organization and assembly in many cell types, however, its significance in adipose tissue is not well characterized. Here, we demonstrate high RhoA activity in adipose tissues of C57BL/6J mice. To determine the effect of RhoA activation on 3T3-L1 cells, stable cell lines overexpressing G14VRhoA fused to destabilizing domain of FKBP12 (DD-G14VRhoA-L1) were generated. Treatment of DD-G14VRhoA-L1 cells with Shield1 following their differentiation into adipocytes, resulted in the appearance of thick cortical actin filaments, and increased the mRNA expression levels of plasminogen activator inhibitor type-1 (PAI-1) and monocyte chemoattractant protein-1 (MCP-1). The induction of PAI-1 and MCP-1 was inhibited by treatment with a Rho-associated kinase (ROCK) inhibitor, Y-27632. In 3T3-L1 adipocytes, tumor necrosis factor-alpha activated RhoA and increased mRNA expression of PAI-1 and MCP-1, and their treatment with Y-27632 partially inhibited these changes. The results indicate that RhoA-ROCK pathway induces inflammatory cytokine expression in adipocytes.
Nakayama
Yuki
Y
Department of Organismal Biosystems, Graduate School of Frontier Biosciences, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
Komuro
Ryutaro
R
Yamamoto
Akiko
A
Miyata
Yugo
Y
Tanaka
Masaki
M
Matsuda
Morihiro
M
Fukuhara
Atsunori
A
Shimomura
Iichiro
I
D016475:3T3 Cells; D017667:Adipocytes / Q000201:enzymology*; D000577:Amides / Q000494:pharmacology; D000818:Animals; D018932:Chemokine CCL2 / Q000096:biosynthesis; D016207:Cytokines / Q000096:biosynthesis*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D058258:Serpin E2; D015843:Serpins / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000037:antagonists & inhibitors / Q000378:metabolism*
D000577:Amides; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D016207:Cytokines; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D058258:Serpin E2; C511869:Serpine2 protein, mouse; D015843:Serpins; D014409:Tumor Necrosis Factor-alpha; C108830:Y 27632; D054460:rho-Associated Kinases; D020742:rhoA GTP-Binding Protein