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Phosphatidic acid as a regulator of matrix metalloproteinase‐9 expression via the TNF‐α signaling pathway
Author(s) -
Lee Jin-Gu,
Lee Sun-Hye,
Park Dae-Weon,
Bae Yoe-Sik,
Yun Sung-Su,
Kim Jae-Ryong,
Baek Suk-Hwan
Publication year - 2007
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2007.01.048
Subject(s) - regulator , phosphatidic acid , microbiology and biotechnology , chemistry , matrix metalloproteinase , signal transduction , tumor necrosis factor alpha , biochemistry , biology , immunology , gene , phospholipid , membrane
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)‐α signaling. We performed antibody array analysis on proteins from macrophages stimulated with PA. PA was found to induce the production of TNF‐α, 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‐α production and MMP‐9 expression. Neutralizing TNF‐α, TNFR1 or TNFR2 antibodies significantly suppressed PA‐induced MMP‐9 expression, suggesting that the production of TNF‐α in response to PA preceded the expression of MMP‐9. Moreover, lipopolysaccharide‐induced PA also led to TNF‐α 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‐α/TNFRs‐dependent signaling pathway.