Adiponectin regulates vascular endothelial growth factor-C expression in macrophages via Syk-ERK pathway.

Abstract

Adiponectin is exclusively expressed in adipose tissues and exhibits protective effects against cardiovascular and metabolic diseases. It enhances AMP-activated kinase (AMPK) and peroxisome proliferator-activated receptor α (PPARα) signaling in the liver and skeletal muscles, however, its signaling pathways in macrophages remain to be elucidated. Here, we show that adiponectin upregulated the expression of vascular endothelial growth factor (VEGF)-C, and induced phosphorylation of extracellular signal-regulated kinase (ERK) in macrophages. Inhibition of Syk abrogated adiponectin-induced VEGF-C expression and ERK phosphorylation. Furthermore, inhibition of ERK blocked the induction of VEGF-C gene. Inhibition of Syk, but not that of ERK, abrogated adiponectin-induced expression of cyclooxygenase (COX)-2, tissue inhibitor of metalloproteinase (TIMP)-1, and interleukin (IL)-6. These results indicate that adiponectin regulates VEGF-C expression via Syk-ERK pathway in macrophages.

• Authors: Di Hu, Atsunori Fukuhara, Yugo Miyata, Chieko Yokoyama, Michio Otsuki, Shinji Kihara, Iichiro Shimomura
• Journal: PloS one (PLoS One) Vol. 8 Issue 2 Pg. e56071 ( 2013) ISSN: 1932-6203 [Electronic] United States
• PMID: 23424645 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 2-(7-(3,4-dimethoxyphenyl)imidazo(1,2-c)pyrimidin-5-ylamino)nicotinamide
• Adiponectin
• Intracellular Signaling Peptides and Proteins
• Protein Kinase Inhibitors
• Pyrimidines
• RNA, Messenger
• Vascular Endothelial Growth Factor C
• Niacinamide
• Protein-Tyrosine Kinases
• SYK protein, human
• Syk Kinase
• Syk protein, mouse
• Extracellular Signal-Regulated MAP Kinases

Topics

• Adiponectin (pharmacology)
• Animals
• Cell Line
• Extracellular Signal-Regulated MAP Kinases (metabolism)
• Gene Expression Regulation (drug effects)
• Humans
• Intracellular Signaling Peptides and Proteins (metabolism)
• Macrophages (cytology, drug effects, metabolism)
• Mice
• Niacinamide (analogs & derivatives, pharmacology)
• Phosphorylation (drug effects)
• Protein Kinase Inhibitors (pharmacology)
• Protein-Tyrosine Kinases (metabolism)
• Pyrimidines (pharmacology)
• RNA, Messenger (genetics, metabolism)
• Signal Transduction (drug effects)
• Syk Kinase
• Transcriptional Activation (drug effects)
• Vascular Endothelial Growth Factor C (genetics)