Fibroblast Growth Factor Signaling in the Vasculature

Yang, Xuehui; Liaw, Lucy; Prudovsky, Igor; Brooks, Peter C.; Vary, Calvin P.H.; Oxburgh, Leif; Friesel, Robert

doi:10.1007/s11883-015-0509-6

Cited by 82 publications

(60 citation statements)

References 103 publications

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“…Although these protein isoforms are identified in pathological conditions like cancer, Alzheimer's disease and atherosclerosis, the mechanisms and significance of ASE-mediated production of isoforms in the pregnant UA are yet to be investigated. It is important to note that the above-mentioned protein isoforms are known to interact with the phosphatidylinositol signaling system, which has a unique physiological role in vascular endothelial and smooth muscle contraction [78][79][80][81][82][83]. Besides, this study revealed that differential splicing occurred in a small subset of DEGs (40 upregulated and 61 downregulated genes), suggesting that splicing may contribute to the differential expression of these genes.…”

Section: Discussionmentioning

confidence: 65%

Whole-Genome Uterine Artery Transcriptome Profiling and Alternative Splicing Analysis in Rat Pregnancy

Gopalakrishnan

Kumar

2020

IJMS

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During pregnancy, the uterine artery (UA) undergoes extensive remodeling to permit a 20-40 fold increase in blood flow with associated changes in the expression of a multitude of genes. This study used next-gen RNA sequencing technology to identify pathways and genes potentially involved in arterial adaptations in pregnant rat UA (gestation day 20) compared with non-pregnant rat UA (diestrus). A total of 2245 genes were differentially expressed, with 1257 up-regulated and 970 down-regulated in pregnant UA. Gene clustering analysis revealed a unique cluster of suppressed genes implicated in calcium signaling pathway and vascular smooth muscle contraction in pregnant UA. Transcription factor binding site motif scanning identified C2H2 ZF, AP-2 and CxxC as likely factors functional on the promoters of down-regulated genes involved in calcium signaling and vascular smooth muscle contraction. In addition, 1686 genes exhibited alternative splicing that were mainly implicated in microtubule organization and smooth muscle contraction. Cross-comparison analysis identified novel genes that were both differentially expressed and alternatively spliced; these were involved in leukocyte and B cell biology and lipid metabolism. In conclusion, this first comprehensive study provides a valuable resource for understanding the molecular mechanism underlying gestational uterine arterial adaptations during pregnancy. RAMP])[15], calcium and potassium channels [16,17], growth factor genes (vascular endothelial growth factor [VEGF], placental growth factor, insulin-like growth factor 1 [IGF-I] and bone morphogenetic protein 6 [BMP6], vasodilator genes (nitric oxide (endothelial nitric oxide synthase), and hydrogen sulfide [cystathionine β-synthase]) [3,18] in uterine vasculature during pregnancy significantly impact vascular remodeling and vasodilation. Furthermore, several other signaling pathways have been implicated in arterial remodeling, including matrix metalloproteinases (MMP) activation [19], adrenergic influences [20], toll-like receptors [21], cytoskeleton [22], including vimentin [23], and membrane-associated tyrosine kinases such as PYK2 [24]. These studies were conducted in isolation, and surprisingly, no studies have comprehensively examined global transcriptome and the associated pathways involved in normal gestational uterine vascular adaptations.Another missing link is whether post-transcriptional regulation also contributes to the functions of key genes that modulate pregnancy mediated uterine vascular adaptations. Although the pre-mRNAs are transcribed from a single gene locus, through the alternative splicing, like differential exon inclusion or skipping, the pre-mRNAs can be spliced into different ways to generate divergent isoforms [25,26]. These new isoforms often result in interaction profiles that are divergent from the 'canonical' isoform [27]. There is only one study that discovered changes in alternative splicing of guanylyl cyclase, a major vasodilatory mediator, in the pregnant ovine UA [28]. Thus, whether...

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Section: Discussionmentioning

confidence: 65%

Whole-Genome Uterine Artery Transcriptome Profiling and Alternative Splicing Analysis in Rat Pregnancy

Gopalakrishnan

Kumar

2020

IJMS

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“…This may be due to the timeframe in which this kinase activity was measured or the single‐cell type evaluated. The importance of FGF2 in angiogenesis has been well established . In one study of FGF‐2 deficient mouse endothelial cells, FGF‐2 activation of ERK signaling was required for cell migration .…”

Section: Discussionmentioning

confidence: 99%

“…The importance of FGF2 in angiogenesis has been well established. 38 In one study of FGF-2 deficient mouse endothelial cells, FGF-2 activation of ERK signaling was required for cell migration. 39 Comparatively little work has been done on CH3L1 (also known as YKL-40, a heparin-binding glycoprotein), but due to its role in cancer, CH3L1 has been characterized in the context of tumor angiogenesis.…”

Section: Discussionmentioning

confidence: 99%

A mechanistic evaluation of the angiogenic properties of a dehydrated amnion chorion membrane in vitro and in vivo

McQuilling

Burnette

Kimmerling

et al. 2019

Wound Repair Regeneration

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Angiogenesis is essential for the successful repair of tissues; however, in many chronic conditions, angiogenesis is inhibited. Placental tissues have been shown to illicit an angiogenic response both in vitro and in vivo, and the angiogenic properties of these tissues likely contribute to observed clinical outcomes. Although there is some work describing the angiogenic effects of these tissues, comparatively little has been done to determine the possible mechanisms responsible for this effect. The purpose of this study was to conduct a thorough evaluation of a commercially available dehydrated amnion chorion membrane to better understand how these tissues may promote angiogenesis. The proteomic content of this tissue was evaluated using a high throughput proteomic microarray, and then the effects of these grafts were evaluated in vivo using subcutaneous gelfoam sponge implants containing conditioned media (CM) from the graft. Human microvascular endothelial cells were then used to determine how released factors effect migration, proliferation, gene expression, and protein production in vitro. Finally, to elucidate potential signaling‐pathways through which tissue‐derived factors act to induce pro‐angiogenetic phenotypes in endothelial cells in vitro, we performed a global analysis of both serine/threonine and tyrosine kinase activity. Kinomic and proteomic data were then combined to generate protein–protein interaction networks that enabled the identification of multiple growth factors and cytokines with both pro‐ and anti‐angiogenetic properties. In vivo, the addition of CM resulted in increased CD31 and αSMA staining and increases in pro‐angiogenic gene expression. In vitro, CM resulted in significant increases in endothelial proliferation, migration, and the expression of granulocyte‐macrophage colony‐stimulating factor, hepatocyte growth factor, and transforming growth factor beta‐3. Integrated kinomic analysis implicated ERK1/2 signaling as the primary pathway activated following culture of endothelial cells with dehydrated amnion/chorion membrane (dACM) CM. In conclusion, dACM grafts triggered pro‐angiogenic responses both in vitro and in vivo that are likely at least partially mediated by ERK1/2 signaling.

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“…Fibroblasts : Another supporting cell that plays a vital role in angiogenesis is the fibroblast, whose primary function is to synthesize and maintain the extracellular matrix, mostly by secreting collagen . In particular, they become activated and secrete various collagens in response to wounding . Fibroblast‐derived matrix proteins such as collagen 1 and procollagen C‐endopeptidase enhancer 1 are critical for the increased stiffness of the extracellular matrix which further induces the vasculature lumen formation .…”

Section: Design Consideration: How Simple Is Complex Enough?mentioning

confidence: 99%

Recreating Physiological Environments In Vitro: Design Rules for Microfluidic‐Based Vascularized Tissue Constructs

Tan

Leung

2020

Small

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Vascularization of engineered tissue constructs remains one of the greatest unmet challenges to mimicking the native tissue microenvironment in vitro. The main obstacle is recapitulating the complexity of the physiological environment while providing simplicity in operation and manipulation of the model. Microfluidic technology has emerged as a promising tool that enables perfusion of the tissue constructs through engineered vasculatures and precise control of the vascular microenvironment cues in vitro. The tunable microenvironment includes i) biochemical cues such as coculture, supporting matrix, and growth factors and ii) engineering aspects such as vasculature engineering methods, fluid flow, and shear stress. In this systematic review, the design considerations of the microfluidic‐based in vitro model are discussed, with an emphasis on microenvironment control to enhance the development of next‐generation vascularized engineered tissues.

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Fibroblast Growth Factor Signaling in the Vasculature

Cited by 82 publications

References 103 publications

Whole-Genome Uterine Artery Transcriptome Profiling and Alternative Splicing Analysis in Rat Pregnancy

Whole-Genome Uterine Artery Transcriptome Profiling and Alternative Splicing Analysis in Rat Pregnancy

A mechanistic evaluation of the angiogenic properties of a dehydrated amnion chorion membrane in vitro and in vivo

Recreating Physiological Environments In Vitro: Design Rules for Microfluidic‐Based Vascularized Tissue Constructs

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