Matrix metalloproteinase-19 inhibits growth of endothelial cells by generating angiostatin-like fragments from plasminogen

0371282 - ÚMG 2012 RIV GB eng J - Článek v odborném periodiku
Brauer, Rena - Beck, Inken - Roderfeld, M. - Roeb, E. - Sedláček, Radislav
Matrix metalloproteinase-19 inhibits growth of endothelial cells by generating angiostatin-like fragments from plasminogen.
BMC Biochemistry. Roč. 12, - (2011), e38. ISSN 1471-2091. E-ISSN 1471-2091
Grant CEP: GA ČR GC301/08/J053; GA ČR GP301/09/P662
Výzkumný záměr: CEZ:AV0Z50520701; CEZ:AV0Z50520514
Klíčová slova: matrix metalloproteinase-19 * angiogenesis * endothelial cells
Kód oboru RIV: EB - Genetika a molekulární biologie
Impakt faktor: 1.988, rok: 2011

We report here that MMP-19 processes human plasminogen in a characteristic cleavage pattern to generate three angiostatin-like fragments with a molecular weight of 35, 38, and 42 kDa. These fragments released by MMP-19 significantly inhibited the proliferation of HMEC cells by 27% (p = 0.01) and reduced formation of capillary-like structures by 45% (p = 0.05) compared with control cells. As it is known that angiostatin blocks hepatocyte growth factor (HGF)-induced pro-angiogenic signaling in endothelial cells due to structural similarities to HGF, we have analyzed if the plasminogen fragments generated by MMP-19 interfere with this pathway. As it involves the activation of c-met, the receptor of HGF, we could show that MMP-19-dependent processing of plasminogen decreases the phosphorylation of c-met. Conclusion: Altogether, MMP-19 exhibits an anti-angiogenic effect on endothelial cells via generation of angiostatin-like fragments.
Trvalý link: http://hdl.handle.net/11104/0204831