scholarly journals Notch signaling and taxis mechanims regulate early stage angiogenesis: A mathematical and computational model

2019 ◽  
Author(s):  
Rocío Vega ◽  
Manuel Carretero ◽  
Rui D.M. Travasso ◽  
Luis L. Bonilla
Keyword(s):  
Mathematical Model ◽  
Wound Healing ◽  
Numerical Simulations ◽  
Notch Signaling ◽  
Blood Vessels ◽  
Crucial Role ◽  
Early Stage ◽  
Tissue Mechanics ◽  
Organ Development

AbstractDuring angiogenesis, new blood vessels sprout and grow from existing ones. This process plays a crucial role in organ development and repair, in wound healing and in numerous pathological processes such as cancer progression or diabetes. Here, we present a mathematical model of early stage angiogenesis that permits exploration of the relative importance of mechanical, chemical and cellular cues. Endothelial cells proliferate and move over an extracellular matrix by following external gradients of Vessel Endothelial Growth Factor, adhesion and stiffness, which are incorporated to a Cellular Potts model with a finite element description of elasticity. The dynamics of Notch signaling involving Delta-4 and Jagged-1 ligands determines tip cell selection and vessel branching. Through their production rates, competing Jagged-Notch and Delta-Notch dynamics determine the influence of lateral inhibition and lateral induction on the selection of cellular phenotypes, branching of blood vessels, anastomosis (fusion of blood vessels) and angiogenesis velocity. Anastomosis may be favored or impeded depending on the mechanical configuration of strain vectors in the ECM near tip cells. Numerical simulations demonstrate that increasing Jagged production results in pathological vasculatures with thinner and more abundant vessels, which can be compensated by augmenting the production of Delta ligands.Author SummaryAngiogenesis is the process by which new blood vessels grow from existing ones. This process plays a crucial role in organ development, in wound healing and in numerous pathological processes such as cancer growth or in diabetes. Angiogenesis is a complex, multi-step and well regulated process where biochemistry and physics are intertwined. The process entails signaling in vessel cells being driven by both chemical and mechanical mechanisms that result in vascular cell movement, deformation and proliferation. Mathematical models have the ability to bring together these mechanisms in order to explore their relative relevance in vessel growth. Here, we present a mathematical model of early stage angiogenesis that is able to explore the role of biochemical signaling and tissue mechanics. We use this model to unravel the regulating role of Jagged, Notch and Delta dynamics in vascular cells. These membrane proteins have an important part in determining the leading cell in each neo-vascular sprout. Numerical simulations demonstrate that increasing Jagged production results in pathological vasculatures with thinner and more abundant vessels, which can be compensated by augmenting the production of Delta ligands.

Role of Leukocytes and Endothelial Cells in the Development of Angiogenesis in Inflammation and Wound Healing

2001 ◽  
Vol 125 (1) ◽  
pp. 67-71 ◽  
Author(s):  
Mark W. Lingen
Keyword(s):  
Wound Healing ◽  
Endothelial Cells ◽  
Blood Vessels ◽  
Peripheral Blood ◽  
Inflammatory Process ◽  
Signs And Symptoms ◽  
Critical Component ◽  
Complex Environment ◽  
Seminal Article

Abstract The basic signs and symptoms of inflammation and wound healing have been appreciated for thousands of years. However, the specific cells involved and their roles in this complex environment are still being elucidated today. In 1926, the origin of the phagocytic mononuclear ameboid wandering cell (macrophage) had not been determined. One popular theory was that the cells were differentiated from the endothelial cells of the nearby blood vessels, whereas others believed that the cells came from the peripheral blood or resting wandering cells. The purpose of this article is to review the seminal article published by Lang regarding this topic nearly 75 years ago. In addition, this article will review what is now known with regard to the role of the macrophage and endothelial cells in the development of angiogenesis, which is arguably the most critical component of successful inflammatory process or wound healing.

INTERLEUKIN MATHEMATICAL MODEL OF AN IMMUNE SYSTEM

1995 ◽  
Vol 03 (03) ◽  
pp. 889-902 ◽  
Author(s):  
URSULA FORYS
Keyword(s):  
Infectious Disease ◽  
Mathematical Model ◽  
Immune System ◽  
Numerical Simulations ◽  
Basic Properties

Some generalizations of Marchuk's model of an infectious disease with respect to the role of interleukins are presented in this paper. Basic properties of the models are studied. Results of numerical simulations with different coefficients corresponding to the different forms of the disease are shown.

scholarly journals Heteronuclear and homonuclear radio-frequency-driven recoupling

2021 ◽  
Vol 2 (1) ◽  
pp. 343-353
Author(s):  
Evgeny Nimerovsky ◽  
Kai Xue ◽  
Kumar Tekwani Movellan ◽  
Loren B. Andreas
Keyword(s):  
Radio Frequency ◽  
Numerical Simulations ◽  
Crucial Role ◽  
Pulse Sequence ◽  
Magic Angle Spinning ◽  
Magic Angle ◽  
Dipolar Interactions ◽  
Phase Cycling ◽  
Angle Spinning

Abstract. The radio-frequency-driven recoupling (RFDR) pulse sequence is used in magic-angle spinning (MAS) NMR to recouple homonuclear dipolar interactions. Here we show simultaneous recoupling of both the heteronuclear and homonuclear dipolar interactions by applying RFDR pulses on two channels. We demonstrate the method, called HETeronuclear RFDR (HET-RFDR), on microcrystalline SH3 samples at 10 and 55.555 kHz MAS. Numerical simulations of both HET-RFDR and standard RFDR sequences allow for better understanding of the influence of offsets and paths of magnetization transfers for both HET-RFDR and RFDR experiments, as well as the crucial role of XY phase cycling.

scholarly journals Epidermal stem cells maintain stemness via a biomimetic micro/nanofiber scaffold that promotes wound healing by activating the Notch signaling pathway

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Zhixiao Lin ◽  
Congying Zhao ◽  
Zhanjun Lei ◽  
Yuheng Zhang ◽  
Rong Huang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Wound Healing ◽  
Notch Signaling ◽  
Signaling Pathway ◽  
Notch Signaling Pathway ◽  
Skin Defect ◽  
Epidermal Stem Cells ◽  
Nanofiber Scaffold ◽  
Related Proteins

Abstract Background Epidermal stem cells (EpSCs) play a vital role in wound healing and skin renewal. Although biomaterial scaffolds have been used for transplantation of EpSCs in wound healing, the ex vivo differentiation of EpSCs limits their application. Methods To inhibit the differentiation of EpSCs and maintain their stemness, we developed an electrospun polycaprolactone (PCL)+cellulose acetate (CA) micro/nanofiber for the culture and transplantation of EpSCs. The modulation effect on EpSCs of the scaffold and the underlying mechanism were explored. Liquid chromatography-tandem mass spectrometry for label-free quantitative proteomics was used to analyze proteomic changes in EpSCs cultured on scaffolds. In addition, the role of transplanted undifferentiated EpSCs in wound healing was also studied. Results In this study, we found that the PCL+CA micro/nanofiber scaffold can inhibit the differentiation of EpSCs through YAP activation-mediated inhibition of the Notch signaling pathway. Significantly differentially expressed proteomics was observed in EpSCs cultured on scaffolds and IV collagen-coated culture dishes. Importantly, differential expression levels of ribosome-related proteins and metabolic pathway-related proteins were detected. Moreover, undifferentiated EpSCs transplanted with the PCL+CA scaffold can promote wound healing through the activation of the Notch signaling pathway in rat full-thickness skin defect models. Conclusions Overall, our study demonstrated the role of the PCL+CA micro-nanofiber scaffold in maintaining the stemness of EpSCs for wound healing, which can be helpful for the development of EpSCs maintaining scaffolds and exploration of interactions between biomaterials and EpSCs.

Article Commentary: Epidermal Wound Healing: The Clinical Implications of a Simple Mathematical Model

1992 ◽  
Vol 1 (5) ◽  
pp. 365-371 ◽  
Author(s):  
Jonathan A. Sherratt ◽  
J.D. Murray
Keyword(s):  
Mathematical Model ◽  
Wound Healing ◽  
Experimental Research ◽  
Healing Time ◽  
Clinical Implications ◽  
Simple Mathematical Model ◽  
New Ideas ◽  
Healing Wounds ◽  
The Subject

The role of biochemical regulation in the healing of epidermal wounds remains the subject of much biological debate. We have previously developed a mathematical model which focusses on the role of mitogenic autoregulation in reepithelialization (23–25). Here, we discuss some predictions of our model and their clinical relevance. We investigate both the effects of adding mitotic regulators to healing wounds and the dependence of healing time on wound shape. The latter study suggests a possible mechanism for the control of changes in wound shape during healing. The predictions we make are amenable to experimental verification, and suggest new ideas for experimental research.

scholarly journals Crucial role of vinexin for keratinocyte migration in vitro and epidermal wound healing in vivo

2010 ◽  
Vol 316 (10) ◽  
pp. 1728-1738 ◽  
Author(s):  
Noriyuki Kioka ◽  
Takuya Ito ◽  
Hiroshi Yamashita ◽  
Natsuko Uekawa ◽  
Tsutomu Umemoto ◽  
...  
Keyword(s):  
Wound Healing ◽  
Crucial Role ◽  
Keratinocyte Migration

Effects of Extracellular Matrices on F9 Teratocarcinoma Stem Cells: A Crucial Role of Type IV Collagen in the Early Stage of Differentiation of F9 Stem Cells

Pathobiology ◽  
2002 ◽  
Vol 70 (4) ◽  
pp. 219-228 ◽  
Author(s):  
Keiko Watanabe ◽  
Shuji Toda ◽  
Nobuhisa Yonemitsu ◽  
Hajime Sugihara
Keyword(s):  
Stem Cells ◽  
Crucial Role ◽  
Type Iv Collagen ◽  
Early Stage ◽  
Extracellular Matrices ◽  
Type Iv ◽  
F9 Teratocarcinoma

scholarly journals Progression of Deoxynivalenol Concentrations in Spikes and Kernels of Winter Wheat Cultivars after Inoculation with Fusarium culmorum

2011 ◽  
Vol 42 (No. 4) ◽  
pp. 137-141 ◽  
Author(s):  
J. Chrpová ◽  
V. Šíp ◽  
E. Matějová ◽  
S. Sýkorová
Keyword(s):  
Winter Wheat ◽  
Fusarium Head Blight ◽  
Crucial Role ◽  
Early Stage ◽  
Fusarium Culmorum ◽  
Wheat Cultivars ◽  
Head Blight ◽  
Winter Wheat Cultivars ◽  
High Concentrations

Progression of deoxynivalenol (DON) concentrations in spikes and kernels was studied in relation to Fusarium head blight (FHB) symptoms in five winter wheat cultivars, differing in resistance to FHB, after single floret inoculation with an aggressive isolate of Fusarium culmorum. After inoculation in field conditions the spikes were detached from the plant and kept in the greenhouse under controlled conditions. High concentrations of DON were detected in susceptible cultivars at an early stage of pathogenesis (7 days after inoculation). Over the whole examined 21-day period and also at maturity spikes contained more DON than kernels. While differences between cultivars in the accumulation of DON were highly expressed already 7 days after inoculation, differences in symptomatic reactions were not clear until day 21. Owing to the reported crucial role of DON at early stages of pathogenesis, the importance of appropriate timing of fungicide application is highly stressed.  

Platelet-induced growth of human fibroblasts is associated with an increased expression of 5-lipoxygenase

2006 ◽  
Vol 96 (11) ◽  
pp. 652-659 ◽  
Author(s):  
Cecilia Berg ◽  
Sven Hammarström ◽  
Helena Herbertsson ◽  
Eva Lindström ◽  
Ann-Charlotte Svensson ◽  
...  
Keyword(s):  
Wound Healing ◽  
Arachidonic Acid ◽  
Crucial Role ◽  
Elevated Level ◽  
Human Fibroblasts ◽  
Inflammatory Factors ◽  
Specific Inhibition ◽  
Rt Pcr ◽  
Activated Platelets

SummaryProliferation of fibroblasts is vital for adequate wound healing but is probably also involved in different hyperproliferative disorders such as atherosclerosis and cancer. The regeneration of tissue usually starts with coagulation, involving release of mitogenic and inflammatory factors from activated platelets. This study focuses on the role of eicosanoids in the proliferative effects of platelets on human fibroblasts. We show that the phospholipase A2 inhibitor 7,7-dimethyl-5,8-eicosadienoic acid (DMDA), the combined cyclooxygenase (COX) and lipoxygenase (LOX) inhibitor 5,8,11,14-eicosatetraynoic acid (ETYA) and the LOX inhibitor 5,8,11-eicosatriynoic acid (ETI) block the platelet-induced proliferation of serum starved subconfluent human fibroblasts. Anti-proliferative effects were also obtained by specific inhibition of 5-LOX with 5,6-dehydro arachidonic acid (5,6-dAA), whereas the 12-LOX inhibitor cinnamyl-3,4-dihydroxy-α-cyanocinnamate (CDC) did not affect the platelet-stimulated growth of fibroblasts. The expression of 5-LOX was analyzed by reverse-transcriptase-mediated PCR (RT-PCR), Western blotting and HPLC. 5-LOX message and protein was detected in fibroblasts but not in platelets. Incubation with platelets markedly increased, already after one hour, the expression of 5-LOX in the fibroblast culture. The increased 5-LOX activity was associated with an elevated level of the 5-LOX metabolite 5-hydroxyeicosatetraenoic acid (5-HETE) reaching its maximum after 1–2 hours of co-incubation of fibroblasts and platelets. The 5-HETE production was reduced by the inhibitors DMDA, ETYA and ETI. In conclusion, this study suggests that platelet-stimulated proliferation of fibroblasts is mediated by an increased 5-LOX activity, which supports recent findings indicating a crucial role for this enzyme in proliferative disorders such as atherosclerosis.

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