Abstract：
:Cysteine cathepsins are a family of proteases involved in intracellular protein turnover and extracellular matrix degradation. Cathepsin B (Ctsb) and cathepsin Z (Ctsz) promote tumorigenesis and Ctsb is a known modulator of tumor angiogenesis. We therefore investigated the angiomodulatory function of these cathepsins in vitro as well as in a mouse model of laser-induced choroidal neovascularization (laser-CNV). Ctsb(-/-), Ctsz(-/-), Ctsb/Ctsz double-knockout (Ctsb/z DKO), and wild type (WT) mice underwent argon laser treatment to induce choroidal neovascularization (CNV). The neovascularized area was quantified individually for each lesion at 14 days after laser coagulation. In vitro the effects of cathepsin inhibitors on angiogenesis were analysed by endothelial cell (EC) spheroid sprouting and EC invadosome assays. Retinas from cathepsin KO mice did not show gross morphological abnormalities. In the laser CNV model, however, Ctsb/z DKO mice displayed a significantly reduced neovascularized area compared to WT (0.027 mm(2) vs. 0.052 mm(2); p = 0.012), while single knockouts did not differ significantly from WT. In line, VEGF-induced EC spheroid sprouting and invadosome formation were not significantly altered by a specific cathepsin B inhibitor alone, but significantly suppressed when more than one cathepsin was inhibited. Our results demonstrate that laser-CNV formation is significantly reduced in Ctsb/z DKO mice. In line, EC sprouting and invadosome formation are blunted when more than one cathepsin is inhibited in vitro. These results reveal an angiomodulatory potential of cathepsins with partial functional redundancies between different cathepsin family members.
journal_name
Exp Eye Resjournal_title
Experimental eye researchauthors
Bühler A,Berger S,Bengsch F,Martin G,Han H,Vierkotten S,Pielen A,Boehringer D,Schlunck G,Fauser S,Agostini HT,Reinheckel T,Stahl Adoi
10.1016/j.exer.2013.06.014subject
Has Abstractpub_date
2013-10-01 00:00:00pages
73-8eissn
0014-4835issn
1096-0007pii
S0014-4835(13)00155-3journal_volume
115pub_type
杂志文章abstract：:Scanning electron microscopy (SEM) of mouse cornea and conjunctiva fixed with picric acid-paraformaldehyde-glutaraldehyde (PA-P-G) mixture revealed a thin layer of amorphous material covering the microvilli of the corneal surface cells. At the transmission electron microscopic (TEM) level, this layer of material stain...
journal_title：Experimental eye research
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更新日期：2020-03-01 00:00:00
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journal_title：Experimental eye research
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doi：10.1006/exer.1994.1068
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doi：10.1016/j.exer.2006.02.011
更新日期：2006-10-01 00:00:00
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pub_type： 杂志文章
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更新日期：2014-07-01 00:00:00
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journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1006/exer.1996.0250
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journal_title：Experimental eye research
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journal_title：Experimental eye research
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journal_title：Experimental eye research
pub_type： 杂志文章
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pub_type： 杂志文章,评审
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更新日期：2016-03-01 00:00:00
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journal_title：Experimental eye research
pub_type： 杂志文章
doi：10.1006/exer.1996.0047
更新日期：1996-04-01 00:00:00
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