Activation of matrix-metalloproteinase-2 and membrane-type-1-matrix-metalloproteinase in endothelial cells and induction of vascular permeability in vivo by human immunodeficiency virus-1 Tat protein and basic fibroblast growth factor.

Tosch E, Barillari G, Sgadari C, Bacigalupo I, Cereseto A, Carlei D, Palladino C, Zietz C, Leone P, Stürzl M, Buttò S, Cafaro A, Monini P, Ensoli B (2001)

Publication Status: Published

Publication Type: Journal article

Publication year: 2001

Journal

Molecular Biology of the Cell American Society for Cell Biology

Book Volume: 12

Pages Range: 2934-46

Journal Issue: 10

DOI: 10.1091/mbc.12.10.2934

Abstract

Previous studies indicated that the Tat protein of human immunodeficiency virus type-1 (HIV-1) is a progression factor for Kaposi's sarcoma (KS). Specifically, extracellular Tat cooperates with basic fibroblast growth factor (bFGF) in promoting KS and endothelial cell growth and locomotion and in inducing KS-like lesions in vivo. Here we show that Tat and bFGF combined increase matrix-metalloproteinase-2 (MMP-2) secretion and activation in endothelial cells in an additive/synergistic manner. These effects are due to the activation of the membrane-type-1-matrix-metalloproteinase and to the induction of the membrane-bound tissue inhibitor of metalloproteinase-2 (TIMP-2) by Tat and bFGF combined, but also to Tat-mediated inhibition of both basal or bFGF-induced TIMP-1 and -2 secretion. Consistent with this, Tat and bFGF promote vascular permeability and edema in vivo that are blocked by a synthetic MMP inhibitor. Finally, high MMP-2 expression is detected in acquired immunodeficiency virus syndrome (AIDS)-KS lesions, and increased levels of MMP-2 are found in plasma from patients with AIDS-KS compared with HIV-uninfected individuals with classic KS, indicating that these mechanisms are operative in AIDS-KS. This suggests a novel pathway by which Tat can increase KS aggressiveness or induce vasculopathy in the setting of HIV-1 infection.

Authors with CRIS profile

Michael Stürzl Professur für Molekulare und Experimentelle Chirurgie

Involved external institutions

Italian National Health Institute / Istituto Superiore di Sanità (ISS) IT Italy (IT) Technische Universität München (TUM) DE Germany (DE)

How to cite

APA:

Tosch, E., Barillari, G., Sgadari, C., Bacigalupo, I., Cereseto, A., Carlei, D.,... Ensoli, B. (2001). Activation of matrix-metalloproteinase-2 and membrane-type-1-matrix-metalloproteinase in endothelial cells and induction of vascular permeability in vivo by human immunodeficiency virus-1 Tat protein and basic fibroblast growth factor. Molecular Biology of the Cell, 12(10), 2934-46. https://doi.org/10.1091/mbc.12.10.2934

MLA:

Tosch, Elena, et al. "Activation of matrix-metalloproteinase-2 and membrane-type-1-matrix-metalloproteinase in endothelial cells and induction of vascular permeability in vivo by human immunodeficiency virus-1 Tat protein and basic fibroblast growth factor." Molecular Biology of the Cell 12.10 (2001): 2934-46.

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