The role of extracellular matrix in mouse and human corneal neovascularization

被引:26
作者
Barbariga, M. [1 ]
Vallone, F. [2 ]
Mosca, E. [3 ]
Bignami, F. [1 ]
Magagnotti, C. [2 ]
Fonteyne, P. [1 ]
Chiappori, F. [3 ]
Milanesi, L. [3 ]
Rama, P. [1 ]
Andolfo, A. [2 ]
Ferrari, G. [1 ]
机构
[1] IRCCS San Raffaele Sci Inst, Eye Repair Lab, Cornea & Ocular Surface Dis Unit, Milan, Italy
[2] IRCCS San Raffaele Sci Inst, Prot Microsequencing Facil, ProMiFa, Milan, Italy
[3] CNR, Inst Biomed Technol, Segrate, MI, Italy
关键词
TENASCIN-C; BINDING-SITE; VEGF-A; FIBRONECTIN; ANGIOGENESIS; LUMICAN; TUMOR; EXPRESSION; PROTEOME; LYMPHANGIOGENESIS;
D O I
10.1038/s41598-019-50718-8
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Corneal neo-vascularization (CNV) is a highly prevalent medical condition which impairs visual acuity. The role of specific proteins in modulating CNV has been extensively reported, although no studies have described the entire human proteome in CNV corneas. In this paper, we performed a proteomic analysis of vascularized vs healthy corneal stroma, in a CNV mouse model and in CNV-affected patients, with a specific focus on extracellular matrix (ECM) proteins. We identified and quantified 2315 murine proteins, 691 human proteins and validated 5 proteins which are differentially expressed in vascularized samples and conserved in mice and humans: tenascin-C and fibronectin-1 were upregulated, while decorin, lumican and collagen-VI were downregulated in CNV samples. Interestingly, among CNV patients, those affected with Acanthamoeba keratitis showed the highest levels of fibronectin-1 and tenascin-C, suggesting a specific role of these two proteins in Acanthamoeba driven corneal CNV. On a broader picture, our findings support the hypothesis that the corneal stroma in CNV samples is disorganized and less compact. We are confident that the dissection of the human corneal proteome may shed new light on the complex pathophysiology of human CNV, and finally lead to improved treatments.
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页数:12
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