scholarly journals The C-terminal tail of polycystin-1 regulates complement factor B expression by signal transducer and activator of transcription 1

2016 ◽  
Vol 310 (11) ◽  
pp. F1284-F1294 ◽  
Author(s):  
Ming Wu ◽  
Meihan Chen ◽  
Ying Jing ◽  
Junhui Gu ◽  
Shuqin Mei ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Promoter Activity ◽  
Dominant Negative ◽  
Conditioned Media ◽  
Complement Factor ◽  
Dependent Manner ◽  
Factor B ◽  
Renal Epithelial Cells ◽  
Complement Factor B ◽  
M2 Phenotype

Inhibition of the overactivated alternative complement pathway in autosomal dominant polycystic kidney disease (ADPKD) retards disease progression in animal models; however, it remains unknown how complement factor B (CFB) is upregulated in ADPKD. Here, we showed that the overexpression of CFB in cystic kidneys is associated with increased JAK2/STAT1 activity and enhanced expression of the polycystin-1 C-terminal tail (PC1-CTT). Overexpression or blockage of STAT1 increased or decreased CFB expression and CFB promoter activity. Moreover, overexpression of PC1-CTT induced JAK2/STAT1 activation and CFB upregulation in renal tubular epithelial cells. Furthermore, PC1-CTT overexpression increased human CFB promoter activity, whereas dominant negative STAT1 plasmids or mutation of putative STAT1 responsive elements decreased PC1-CTT-induced CFB promoter activity. The effect of CFB on macrophage differentiation was tested on a mouse macrophage cell line. Bioactive CFB dose dependently promoted macrophage M2 phenotype conversion. In addition, conditioned media from renal epithelial cells promoted macrophage M2 phenotype conversion which was blocked by STAT1 inhibition in a dose-dependent manner. Conditioned media from PC1-CTT-transfected renal epithelial cells further promoted macrophage M2 phenotype conversion, which was suppressed by fludarabine or a CFB antibody. In addition, we show that NF-κB acts downstream of PC1-CTT and may partly mediate PC1-CTT-induced CFB expression. In conclusion, our study reveals possible mechanisms of CFB upregulation in ADPKD and a novel role of PC1-CTT in ADPKD-associated inflammation. Furthermore, our study suggests that targeting STAT1 may be a new strategy to prevent inflammation in the kidney of patients with ADPKD.

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

2021 ◽  
Vol 22 (17) ◽  
pp. 9580
Author(s):  
Hannah Murray ◽  
Beiying Qiu ◽  
Sze Yuan Ho ◽  
Xiaomeng Wang
Keyword(s):  
Signaling Pathway ◽  
Alternative Pathway ◽  
Complement Factor ◽  
Dependent Manner ◽  
Factor B ◽  
Ocular Angiogenesis ◽  
Complement Factor B ◽  
Ocular Neovascularization ◽  
Vegf Signaling ◽  
Vegf Signaling Pathway

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.

scholarly journals Plasma protein expression profiles, cardiovascular disease, and religious struggles among South Asians in the MASALA study

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Long H. Ngo ◽  
M. Austin Argentieri ◽  
Simon T. Dillon ◽  
Blake Victor Kent ◽  
Alka M. Kanaya ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Plasma Protein ◽  
Expression Profiles ◽  
South Asians ◽  
Predictive Biomarkers ◽  
Information Criteria ◽  
Blood Protein ◽  
Complement Factor ◽  
Factor B ◽  
Complement Factor B

AbstractBlood protein concentrations are clinically useful, predictive biomarkers of cardiovascular disease (CVD). Despite a higher burden of CVD among U.S. South Asians, no CVD-related proteomics study has been conducted in this sub-population. The aim of this study is to investigate the associations between plasma protein levels and CVD incidence, and to assess the potential influence of religiosity/spirituality (R/S) on significant protein-CVD associations, in South Asians from the MASALA Study. We used a nested case–control design of 50 participants with incident CVD and 50 sex- and age-matched controls. Plasma samples were analyzed by SOMAscan for expression of 1305 proteins. Multivariable logistic regression models and model selection using Akaike Information Criteria were performed on the proteins and clinical covariates, with further effect modification analyses conducted to assess the influence of R/S measures on significant associations between proteins and incident CVD events. We identified 36 proteins that were significantly expressed differentially among CVD cases compared to matched controls. These proteins are involved in immune cell recruitment, atherosclerosis, endothelial cell differentiation, and vascularization. A final multivariable model found three proteins (Contactin-5 [CNTN5], Low affinity immunoglobulin gamma Fc region receptor II-a [FCGR2A], and Complement factor B [CFB]) associated with incident CVD after adjustment for diabetes (AUC = 0.82). Religious struggles that exacerbate the adverse impact of stressful life events, significantly modified the effect of Contactin-5 and Complement factor B on risk of CVD. Our research is this first assessment of the relationship between protein concentrations and risk of CVD in a South Asian sample. Further research is needed to understand patterns of proteomic profiles across diverse ethnic communities, and the influence of resources for resiliency on proteomic signatures and ultimately, risk of CVD.

scholarly journals The effects of metal ions and temperature on the interaction of cobra venom factor and human complement factor B.

1986 ◽  
Vol 261 (24) ◽  
pp. 11038-11044 ◽  
Author(s):  
P Hensley ◽  
M C O'Keefe ◽  
C J Spangler ◽  
J C Osborne ◽  
C W Vogel
Keyword(s):  
Metal Ions ◽  
Cobra Venom ◽  
Complement Factor ◽  
Human Complement ◽  
Cobra Venom Factor ◽  
Factor B ◽  
Complement Factor B

C3 Glomerulonephritis Associated With Complement Factor B Mutation

2015 ◽  
Vol 65 (3) ◽  
pp. 520-521 ◽  
Author(s):  
Sanjeev Sethi ◽  
Richard J.H. Smith ◽  
John J. Dillon ◽  
Fernando C. Fervenza
Keyword(s):  
Complement Factor ◽  
C3 Glomerulonephritis ◽  
Factor B ◽  
Complement Factor B

scholarly journals The Association Between Complement Component 2/Complement Factor B Polymorphisms and Age-related Macular Degeneration: A HuGE Review and Meta-Analysis

2012 ◽  
Vol 176 (5) ◽  
pp. 361-372 ◽  
Author(s):  
Ammarin Thakkinstian ◽  
Mark McEvoy ◽  
Usha Chakravarthy ◽  
Subhabrata Chakrabarti ◽  
Gareth J. McKay ◽  
...  
Keyword(s):  
Macular Degeneration ◽  
Meta Analysis ◽  
Complement Component ◽  
Age Related Macular Degeneration ◽  
Complement Factor ◽  
Factor B ◽  
Complement Factor B ◽  
Age Related

scholarly journals Fibroblast Growth Factors Regulate Prolactin Transcription via an Atypical Rac-Dependent Signaling Pathway

2003 ◽  
Vol 17 (10) ◽  
pp. 1921-1930 ◽  
Author(s):  
Twila A. Jackson ◽  
David M. Koterwas ◽  
Melissa A. Morgan ◽  
Andrew P. Bradford
Keyword(s):  
Gene Expression ◽  
Growth Factors ◽  
Signaling Pathway ◽  
Promoter Activity ◽  
Fibroblast Growth Factors ◽  
Dominant Negative ◽  
Pituitary Cells ◽  
Dependent Manner ◽  
Fibroblast Growth ◽  
Prl Gene

Abstract Fibroblast growth factors (FGFs) play a critical role in pituitary development and in pituitary tumor formation and progression. We have previously characterized FGF signal transduction and regulation of the tissue-specific rat prolactin (rPRL) promoter in GH4 pituitary cells. FGF induction of rPRL transcription is independent of Ras, but mediated by a protein kinase C-δ (PKCδ)-dependent activation of MAPK (ERK). Here we demonstrate a functional role for the Rho family monomeric G protein, Rac1, in FGF regulation of PRL gene expression via an atypical signaling pathway. Expression of dominant negative Rac, but not RhoA or Cdc42, selectively inhibited FGF-induced rPRL promoter activity. Moreover, expression of dominant negative Rac also attenuated FGF-2 and FGF-4 stimulation of MAPK (ERK). However, in contrast to other Rac-dependent signaling pathways, FGF activation of rPRL promoter activity was independent of the c-Jun N-terminal kinase (JNK) and phosphoinositide 3-kinase/Akt cascades. FGFs failed to activate JNK1 or JNK2, and expression of dominant negative JNK or Akt constructs did not block FGF-induced PRL transcription. Consistent with the role of PKCδ in FGF regulation of PRL gene expression, activation of the rPRL promoter was blocked by an inhibitor of phospholipase Cγ (PLCγ) activity. FGF treatment also induced rapid tyrosine phosphorylation of PLCγ in a Rac-dependent manner. These results suggest that FGF-2 and FGF-4 activate PRL gene expression via a novel Rac1, PLCγ, PKCδ, and ERK cascade, independent of phosphoinositol-3-kinase and JNK.

scholarly journals Interplay between complement factor B and Toll‐like receptors and its role in septic cardiomyopathy

2013 ◽  
Vol 27 (S1) ◽  
Author(s):  
Lin Zou ◽  
Yan Li ◽  
Yan Feng ◽  
Ming Zhang ◽  
Chan Chen ◽  
...  
Keyword(s):  
Septic Cardiomyopathy ◽  
Complement Factor ◽  
Toll Like Receptors ◽  
Factor B ◽  
Complement Factor B
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