To investigate whether focal adhesion kinase (FAK) can participate in the secretion of matrix metalloproteinase 9 (MMP9) after CD147 stimulation in THP-1 induced macrophages; thus, to explore the potential treatment perspectives for acute coronary syndrome (ACS).Phorbol-12-myristate-13-acetate (PMA) was used to induce THP-1 cells to differentiate into macrophages. To confirm the peak mRNA and protein expression of FAK and MMP9 after the stimulation of CD147, the macrophages were divided into 5 groups (0, 3, 6, 9, and 12 hours), with 0 hours group as control group. To investigate the role of FAK in the secretion of MMP9, with stimulation of CD147 for 9 hours, FAK inhibitor 14 was used to inhibit FAK Y397 phosphorylation. The mRNA and protein expressions were quantified by qRT-PCR and western blotting, respectively. (1) Relative mRNA expression of FAK and MMP9 were both significantly up-regulated (all P < 0.05) after stimulation of CD147, FAK peaked at 9 hours (3.908 ± 0.106 versus 1, P < 0.05), whereas MMP9 peaked at 6 hours (2.522 ± 0.062 versus 1, P < 0.05). (2) Relative protein expression of FAK, pFAK, and MMP9 were all significantly increased after CD147 stimulation (all P < 0.05), FAK (1.930 ± 0.024 versus 1, P < 0.05) and pFAK (1.737 ± 0.021 versus 1, P < 0.05) peaked at 9 hours, whereas MMP9 peaked at 6 hours (1.527 ± 0.033 versus 1, P < 0.05). (3) CD147 up-regulates FAK, pFAK, and MMP9 mRNA and protein expressions in a dose-dependent manner. (4) FAK inhibitor 14 significantly reduced the relative protein expression level of pFAK (0.077 ± 0.012 versus 1, P < 0.05) and MMP9 (0.133 ± 0.012) at 9 hours after CD147 stimulation.The results demonstrated that FAK Y397 phosphorylation was involved in the secretion of MMP9 after CD147 stimulation in macrophages and may play a role in the regulation of ACS.
Keywords: Acute coronary syndrome; Antigens; Focal adhesion protein-tyrosine kinases.