Complement Factor B Mediates Ocular Angiogenesis through Regulating the VEGF Signaling Pathway

2021 ◽  
Vol 22 (17) ◽  
pp. 9580
Hannah Murray ◽  
Beiying Qiu ◽  
Sze Yuan Ho ◽  
Xiaomeng Wang

Complement factor B (CFB), a 95-kDa protein, is a crucial catalytic element of the alternative pathway (AP) of complement. After binding of CFB to C3b, activation of the AP depends on the proteolytic cleavage of CFB by factor D to generate the C3 convertase (C3bBb). The C3 convertase contains the catalytic subunit of CFB (Bb), the enzymatic site for the cleavage of a new molecule of C3 into C3b. In addition to its role in activating the AP, CFB has been implicated in pathological ocular neovascularization, a common feature of several blinding eye diseases, however, with somewhat conflicting results. The focus of this study was to investigate the direct impact of CFB on ocular neovascularization in a tightly controlled environment. Using mouse models of laser-induced choroidal neovascularization (CNV) and oxygen-induced retinopathy (OIR), our study demonstrated an increase in CFB expression during pathological angiogenesis. Results from several in vitro and ex vivo functionality assays indicated a promoting effect of CFB in angiogenesis. Mechanistically, CFB exerts this pro-angiogenic effect by mediating the vascular endothelial growth factor (VEGF) signaling pathway. In summary, we demonstrate compelling evidence for the role of CFB in driving ocular angiogenesis in a VEGF-dependent manner. This work provides a framework for a more in-depth exploration of CFB-mediated effects in ocular angiogenesis in the future.

2015 ◽  
Vol 65 (3) ◽  
pp. 520-521 ◽  
Sanjeev Sethi ◽  
Richard J.H. Smith ◽  
John J. Dillon ◽  
Fernando C. Fervenza

2011 ◽  
Vol 140 (1-2) ◽  
pp. 170-174 ◽  
Jinyi Qin ◽  
Kylie Munyard ◽  
Chee Y. Lee ◽  
John D. Wetherall ◽  
David M. Groth

1986 ◽  
Vol 261 (24) ◽  
pp. 11038-11044 ◽  
P Hensley ◽  
M C O'Keefe ◽  
C J Spangler ◽  
J C Osborne ◽  
C W Vogel

1996 ◽  
Vol 50 (2) ◽  
pp. 521-525 ◽  
Thomas R. Welch ◽  
Linda S. Beischel ◽  
Marie Frenzke ◽  
David Witte

1991 ◽  
Vol 274 (2) ◽  
pp. 473-480 ◽  
M A Niemann ◽  
A S Bhown ◽  
E J Miller

Accumulating amino acid sequence data have made it increasingly evident that many essential complement proteins have potentially modifiable lysine residues in putative critical functional regions. Evidence is now presented that glucose is covalently attached to lysine-266 of purified human complement Factor B as a result of glycation. Purified B was treated with NaB3H4, which reduces such bound glucose to a mixture of radiolabelled hexitols. Amino acid analysis revealed the expected radiolabelled hexitol-lysine epimers. In addition, fluorography of dried gels resolving the major high-molecular-mass h.p.l.c.-fractionated CNBr-cleavage peptides of NaB3H4-reduced B indicated that this radioactivity was specifically associated with the 15 kDa fragment derived from the N-terminal region of fragment Bb. Amino acid sequence analysis suggested that the C-terminal lysine (residue 266 of B) of the N-terminal Lys-Lys doublet of this peptide is preferentially modified. If such glycation can subsequently be shown to occur in vivo, then perhaps this modification might also be found to affect the functional activity of B and offer a potential explanation for some of the immunopathological complications of diseases exposing key plasma proteins, such as this active-site-containing proteinase of the multimeric alternative-complement-pathway C3/C5 convertases, to long-term high concentrations of glucose, such as the decreased resistance to infection and impaired chemotaxis and phagocytosis characteristic of diabetes.

1998 ◽  
Vol 47 (4) ◽  
pp. 375-380 ◽  
Pekna ◽  
Hietala ◽  
Landin ◽  
Nilsson ◽  
Lagerberg ◽  

2006 ◽  
Vol 104 (1) ◽  
pp. 240-245 ◽  
E. G. de Jorge ◽  
C. L. Harris ◽  
J. Esparza-Gordillo ◽  
L. Carreras ◽  
E. A. Arranz ◽  

2000 ◽  
Vol 275 (1) ◽  
pp. 378-385 ◽  
Yuanyuan Xu ◽  
Antonella Circolo ◽  
Hua Jing ◽  
Yue Wang ◽  
Sthanam V. L. Narayana ◽  

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