Phosphatidic acid as a regulator of matrix metalloproteinase-9 expression via the TNF-alpha signaling pathway |
| |
Authors: | Lee Jin-Gu Lee Sun-Hye Park Dae-Weon Bae Yoe-Sik Yun Sung-Su Kim Jae-Ryong Baek Suk-Hwan |
| |
Affiliation: | Department of Biochemistry & Molecular Biology, Aging-Associated Vascular Disease Research Center, Yeungnam University, Daegu 705-717, Republic of Korea. |
| |
Abstract: | Phosphatidic acid (PA) is implicated in pathophysiological processes associated with cellular signaling events and inflammation, which include the expressional regulation of numerous genes. Here, we show that PA stimulation increases matrix metalloproteinase-9 (MMP-9) expression in macrophages through tumor necrosis factor (TNF)-alpha signaling. We performed antibody array analysis on proteins from macrophages stimulated with PA. PA was found to induce the production of TNF-alpha, but not of TNF receptor (TNFR)1 and TNFR2 in a time-dependent manner and stimulated significant, though delayed, MMP-9 expression. PA induced the phosphorylations of both ERK1/2 and p38, but not of c-jun amino-terminal kinase. Moreover, only ERK1/2 inhibition by U0126 suppressed PA-induced TNF-alpha production and MMP-9 expression. Neutralizing TNF-alpha, TNFR1 or TNFR2 antibodies significantly suppressed PA-induced MMP-9 expression, suggesting that the production of TNF-alpha in response to PA preceded the expression of MMP-9. Moreover, lipopolysaccharide-induced PA also led to TNF-alpha release and resulted in MMP-9 expression. Taken together, these observations suggest that PA may play a role in MMP-9 regulation through ERKs/TNF-alpha/TNFRs-dependent signaling pathway. |
| |
Keywords: | PA, phosphatidic acid lysoPA, lysophosphatidic acid DAG, diacylglycerol PLD, phospholipase D mTOR, mammalian target of rapamycin IL, interleukin ERK, extracellular signal-regulated kinase ECM, extracellular matrix MMP, matrix metalloproteinase TNF, tumor necrosis factor MAPK, mitogen activated protein kinase C8-PA, 1,2-dioctanoyl-glycero-3-phosphate TNFR, TNF receptor JNK, c-jun amino-terminal kinase LPS, lipopolysaccharide |
本文献已被 ScienceDirect PubMed 等数据库收录! |
|