Please use this identifier to cite or link to this item: http://repositorio.unifesp.br/handle/11600/39043
Title: Corneal angiogenesis modulation by cysteine cathepsins: in vitro and in vivo studies
Authors: Coppini, Larissa Pereira [UNIFESP]
Visniauskas, Bruna [UNIFESP]
Costa, Elaine F.
Filho, Milton N. [UNIFESP]
Rodrigues, Eduardo B. [UNIFESP]
Chagas, Jair R. [UNIFESP]
Farah, Michel E. [UNIFESP]
Barros, Nilana M. T. [UNIFESP]
Carmona, Adriana K. [UNIFESP]
Universidade Federal de São Paulo (UNIFESP)
Univ Fed Maranhao
Keywords: Cysteine proteases
Plasminogen
Ocular angiogenesis
Cathepsins
Issue Date: 1-May-2015
Publisher: Elsevier B.V.
Citation: Experimental Eye Research. London: Academic Press Ltd- Elsevier B.V., v. 134, p. 39-46, 2015.
Abstract: Corneal avascularization is essential for normal vision. Several antiangiogenic factors were identified in cornea such as endostatin and angiostatin. Cathepsin V, which is highly expressed in the cornea, can hydrolyze human plasminogen to release angiostatin fragments. Herein, we describe a detailed investigation of the expression profile of cathepsins B, L, S and V in the human cornea and the role of cysteine peptidases in modulating angiogenesis both in vitro and in vivo. We used various methodological tools for this purpose, including real-time PCR, SDS-PAGE, western blotting, catalytic activity assays, cellular assays and induction of corneal neovascularity in rabbit eyes. Human corneal enzymatic activity assays revealed the presence of cysteine proteases that were capable of processing endogenous corneal plasminogen to produce angiostatin-like fragments. Comparative real-time analysis of cathepsin B, L, S and V expression revealed that cathepsin V was the most highly expressed, followed by cathepsins L, B and S. However, cathepsin V depletion revealed that this enzyme is not the major cysteine protease responsible for plasminogen degradation under non-pathological conditions. Furthermore, western blotting analysis indicated that only cathepsins B and S were present in their enzymatically active forms. in vivo analysis of angiogenesis demonstrated that treatment with the cysteine peptidase inhibitor E64 caused a reduction in neovascularization. Taken together, our results show that human corneal cysteine proteases are critically involved in angiogenesis. (C) 2015 Elsevier B.V. All rights reserved.
URI: http://repositorio.unifesp.br/handle/11600/39043
ISSN: 0014-4835
Other Identifiers: http://dx.doi.org/10.1016/j.exer.2015.03.012
Appears in Collections:Em verificação - Geral

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