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  • Title: MMP-2 inhibits PCSK9-induced degradation of the LDL receptor in Hepa1-c1c7 cells.
    Author: Wang X, Berry E, Hernandez-Anzaldo S, Sun D, Adijiang A, Li L, Zhang D, Fernandez-Patron C.
    Journal: FEBS Lett; 2015 Feb 13; 589(4):490-6. PubMed ID: 25613181.
    Abstract:
    Low-density lipoprotein receptor (LDLR) catalyzes the uptake of LDL-cholesterol by liver and peripheral organs. The function of the LDLR is antagonized by pro-protein convertase subtilisin/kexin type 9 (PCSK9), which binds to LDLR at the plasma membrane inducing LDLR degradation. Here, we report that matrix metalloproteinase-2 (MMP-2) interacts with and cleaves PCSK9, as evidenced by proteomic, chemical cross-linkage, blue native-PAGE and domain-specific antibodies Western blot analyses. Furthermore, MMP-2 overexpression renders Hepa1-c1c7 cells resistant to PCSK9-induced LDLR degradation. The data suggest that pathological MMP-2 overexpression may protect the LDLR from PCSK-9-induced degradation.
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