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The Role of p38 MAP Kinase in the Regulation of Tube Formation from Endothelial Cells in a Three‐Dimensional Cell Culture System
Author(s) -
Rajan Suja,
Ye Janming,
Huang Faqing,
Guo Yanlin
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a14-c
Subject(s) - microbiology and biotechnology , matrix metalloproteinase , angiogenesis , matrix (chemical analysis) , phosphorylation , extracellular matrix , protein kinase a , p38 mitogen activated protein kinases , signal transduction , kinase , chemistry , biology , biochemistry , cancer research , chromatography
When cultured in a 3‐dimensional (3D) collagen matrix, endothelial cells undergo a series of morphological changes and form tube‐like structures. This process mimics the steps of vessel formation during angiogenesis. Our previous study has shown that p38 mitogen activated protein kinase (p38) plays multiple roles in tube formation in 3D collagen matrices. We report here that inhibition of p38 by a pharmaceutical inhibitor SB203580 caused cell elongation but inhibited vacuole/tub formation. This result was at least partially due to the inhibited phosphorylation of heat shock protein 27 (HSP27), which is known to regulate the cytoskeleton structure and cell morphology through phosphorylation by the p38 signaling pathway. Treatment of cells with SB203580 also resulted in a significant increase of matrix metalloproteinase (MMP)‐1 and MMP‐9 activity and expression, as determined by zymography analysis and by quantitative PCR, respectively. Recent studies indicated that degradation of collagen matrix by MMP‐1 and MMP‐9 affect matrix stability and causes vessel regression. Together our results indicate that p38 MAP kinase not only regulates intracellular signaling pathways that control cell morphogenesis, but also affects the secretion of MMPs that control the stability of collagen matrix. Using RNA interference method, our preliminary results indicate that both p38α and p38β isoforms play essential roles in these processes during tube formation [Supported by grants NIH R15HL081126].