Vascular endothelial growth factor-D mediates fibrogenic response in myofibroblasts

Zhao, Tian; Zhao, Wenyuan; Wei, Meng; Liu, Chang; Chen, Yuanjian; Bhattacharya, Syamal K.; Sun, Yao

doi:10.1007/s11010-015-2646-1

Cited by 23 publications

(11 citation statements)

References 35 publications

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“…VEGF-C and VEGF-D also serve as profibrogenic mediators that promote tissue fibrosis. 24,25 In this study, we observed significantly increased expression of VEGF-D ( Figure 3e) and VEGFR-3 ( Figure 3f) in the kidney of ALDO-treated rats. However, Ang1-7 co-treatment did not modify renal gene expression of VEGF-D and VEGFR-3 in ALDO-treated rats.…”

Section: Gene Expression Of Fibrotic Mediators In the Kidneysupporting

confidence: 60%

Molecular and Cellular Effect of Angiotensin 1–7 on Hypertensive Kidney Disease

Chen

Zhao

Liu

et al. 2019

American Journal of Hypertension

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Angiotensin-converting enzyme/angiotensin II/type 1 angiotensin receptors (ACE/AngII/AT1) axis of the renninangiotensin system plays an integral role in maintaining vascular tone, salt and water homeostasis, as well as cardiac function in humans. Chronic activation of AngII/AT1 causes hypertension accompanied by cardiac, renal, and vascular injury with remodeling that eventually leads to end-organ damage, such as renal failure, heart failure, and coronary artery disease. 1 During the last decade, classical view of the renninangiotensin system has been challenged by the discovery of ACE2. This membrane-bound enzyme has been identified in rodents and humans, and is found mainly in the heart and kidney. 2 The major role of ACE2 is to cleave AngII to generate Ang1-7. The biological effects of Ang1-7 in the kidney are primarily mediated by interaction with the G-proteincoupled receptor Mas. However, other complex effects have been described that may involve receptor-receptor interactions with AT1 or type 2 angiotensin receptors (AT2) receptors, as well as nuclear receptor binding. 3 The ACE2/Ang1-7/Mas axis counterbalances the role of ACE/ AngII/AT1 axis, thus imparting broader influences on the cardiovascular system, including vasodilatation, myocardial protection, antiarrhythmic effects, and inhibition of pathological cardiac remodeling. 4 Furthermore, a number of experimental findings suggest that Ang1-7 also plays a protective role in the kidney. 5,6 Hypertensive kidney disease is a clinical condition that causes damage to the kidney because of chronic high blood pressure. The renal pathological changes are gradual and progressive, characterized by glomerular damage, followed by glomerular sclerosis and interstitial fibrosis. 7 The intensity of fibrosis correlates with the degree of glomerular filtration deficit. Multiple factors, including Ang1-7, have been shown to contribute to the renal pathological changes. Ang1-7 is reported to attenuate fibrosis in liver, skeletal muscle, and heart. 8 A growing body of evidence supports a role for endogenous or exogenous Ang1-7 serving as a protectant

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Section: Gene Expression Of Fibrotic Mediators In the Kidneysupporting

confidence: 60%

Molecular and Cellular Effect of Angiotensin 1–7 on Hypertensive Kidney Disease

Chen

Zhao

Liu

et al. 2019

American Journal of Hypertension

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“…Figf, also known as Vegfd, is a member of the platelet-derived growth factor/vascular endothelial growth factor (PDGF/VEGF) family and is important for angiogenesis, lymphangiogenesis, and EC growth. It also stimulates myofibroblast growth and collagen synthesis (121). Chrdl1 codes an antagonist of Bmp4.…”

Section: Discussionmentioning

confidence: 99%

Comparative gene array analyses of severe elastic fiber defects in late embryonic and newborn mouse aorta

Staiculescu

Cocciolone

Procknow

et al. 2018

Physiological Genomics

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Elastic fibers provide reversible elasticity to the large arteries and are assembled during development when hemodynamic forces are increasing. Mutations in elastic fiber genes are associated with cardiovascular disease. Mice lacking expression of the elastic fiber genes elastin ( Eln−/−), fibulin-4 ( Efemp2−/−), or lysyl oxidase ( Lox−/−) die at birth with severe cardiovascular malformations. All three genetic knockout models have elastic fiber defects, aortic wall thickening, and arterial tortuosity. However, Eln−/− mice develop arterial stenoses, while Efemp2−/− and Lox−/− mice develop ascending aortic aneurysms. We performed comparative gene array analyses of these three genetic models for two vascular locations and developmental stages to determine differentially expressed genes and pathways that may explain the common and divergent phenotypes. We first examined arterial morphology and wall structure in newborn mice to confirm that the lack of elastin, fibulin-4, or lysyl oxidase expression provided the expected phenotypes. We then compared gene expression levels for each genetic model by three-way ANOVA for genotype, vascular location, and developmental stage. We found three genes upregulated by genotype in all three models, Col8a1, Igfbp2, and Thbs1, indicative of a common response to severe elastic fiber defects in developing mouse aorta. Genes that are differentially regulated by vascular location or developmental stage in all three models suggest mechanisms for location or stage-specific disease pathology. Comparison of signaling pathways enriched in all three models shows upregulation of integrins and matrix proteins involved in early wound healing, but not of mature matrix molecules such as elastic fiber proteins or fibrillar collagens.

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“…A controlled apoptosis and a tidy epithelia-stroma interaction should occur at involved and uninvolved surrounding tissues 36,37 . Some recent evidence suggested that experimental inhibition of angiogenesis ameliorates the development of liver fibrosis, while other recent studies indicate that neutralization or genetic ablation of VEGF can delay tissue repair and fibrosis resolution in damaged tissues 38,39 . The imbalance between pro/anti-angiogenic mediators might contribute to apoptotic or sustain the process of fibrosis, as observed for CCN1/CYR61 involved in attenuating and/or scavenging of TGFβ, mitigating the process of fibrogenesis 13,40,41 .…”

Section: Discussionmentioning

confidence: 99%

Nerve Growth Factor (NGF) modulates in vitro induced myofibroblasts by highlighting a differential protein signature

Esposito

Balzamino

Stigliano

et al. 2021

Sci Rep

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We previously described the profibrogenic effect of NGF on conjunctival Fibroblasts (FBs) and its ability to trigger apoptosis in TGFβ1-induced myofibroblasts (myoFBs). Herein, cell apoptosis/signalling, cytokines’ signature in conditioned media and inflammatory as well as angiogenic pathway were investigated. Experimental myoFBs were exposed to NGF (0.1–100 ng/mL), at defined time-point for confocal and biomolecular analysis. Cells were analysed for apoptotic and cell signalling activation in cell extracts and for some inflammatory and proinflammatory/angiogenic factors’ activations. NGF triggered cJun overexpression and phospho-p65-NFkB nuclear translocation. A decreased Bcl2:Bax ratio and a significant expression of smad7 were confirmed in early AnnexinV-positive myoFBs. A specific protein signature characterised the conditioned media: a dose dependent decrease occurred for IL8, IL6 while a selective increase was observed for VEGF and cyr61 (protein/mRNA). TIMP1 levels were unaffected. Herein, NGF modulation of smad7, the specific IL8 and IL6 as well as VEGF and cyr61 modulation deserve more attention as opening to alternative approaches to counteract fibrosis.

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Vascular endothelial growth factor-D mediates fibrogenic response in myofibroblasts

Cited by 23 publications

References 35 publications

Molecular and Cellular Effect of Angiotensin 1–7 on Hypertensive Kidney Disease

Molecular and Cellular Effect of Angiotensin 1–7 on Hypertensive Kidney Disease

Comparative gene array analyses of severe elastic fiber defects in late embryonic and newborn mouse aorta

Nerve Growth Factor (NGF) modulates in vitro induced myofibroblasts by highlighting a differential protein signature

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