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Related Concept Videos

Canonical Wnt Signaling Pathway02:54

Canonical Wnt Signaling Pathway

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The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which...
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Wnt is a zygotic effect gene that is expressed during very early embryonic development. It regulates various processes in animals starting from early development through the adult stage, such as organogenesis in the embryo and maintenance of neuronal and blood stem cells. Wnt proteins can induce a wide variety of intracellular pathways depending upon the specific abilities of different Wnt ligands to form a complex with shared and cognate receptors in the presence of different co-receptors. The...
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Role Of Notch Signalling In Intestinal Stem Cell Renewal01:12

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Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
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Regulation of Angiogenesis and Blood Supply01:24

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Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
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Notch Signaling Pathway03:14

Notch Signaling Pathway

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The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not...
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Hedgehog Signaling Pathway02:33

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The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...
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Modeling Paracrine Noncanonical Wnt Signaling In Vitro
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Heparanase modulation by Wingless/INT (Wnt).

Carina Mucciolo Melo1,2, Helena Bonciani Nader1, Giselle Zenker Justo1,3

  • 1Department of Biochemistry, Universidade Federal de São Paulo, Rua Três de Maio, 100, 4a. andar, Biologia Molecular, São Paulo, SP, 04044-020, Brazil.

Molecular Biology Reports
|April 23, 2021
PubMed
Summary
This summary is machine-generated.

Heparin, a substrate of heparanase, upregulates heparanase expression through the Wnt/beta-catenin pathway. This finding reveals a novel regulatory mechanism for heparanase, an enzyme crucial in cell signaling and disease.

Keywords:
Cell signallingGlycosaminoglycansHeparan sulfateHeparanase regulationHeparanase-1Heparin

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Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Background:

  • Heparanase is a key enzyme cleaving heparan sulfate/heparin, influencing cell proliferation, migration, inflammation, and carcinogenesis.
  • Heparanase regulation is not fully understood, despite its known inactive 65 kDa precursor and active 50 kDa form.

Purpose of the Study:

  • To investigate if heparanase is regulated by its substrate, heparin.
  • To elucidate the signaling pathway involved in heparin-mediated heparanase regulation.

Main Methods:

  • Chinese hamster ovary (CHO-K1) cells treated with varying doses of heparin.
  • Analysis of heparanase expression via Real-time PCR and flow cytometry.
  • Measurement of heparanase activity using a biotinylated heparan sulfate-coated plate assay.
  • Assessment of Wnt/beta-catenin pathway activation using TCF-driven luciferase activity.
  • Validation using lithium chloride to activate the Wnt/beta-catenin pathway in zebrafish embryos and CHO-K1 cells.

Main Results:

  • Exogenous heparin treatment significantly increased heparanase mRNA and protein levels in CHO-K1 cells.
  • The Wnt/beta-catenin pathway was identified as a key mediator in enhancing heparanase expression upon heparin treatment.
  • Lithium chloride treatment confirmed the involvement of the Wnt/beta-catenin pathway in regulating heparanase in vitro and in vivo.

Conclusions:

  • Heparin modulates heparanase expression through the Wnt/beta-catenin signaling pathway.
  • This study uncovers a novel feedback mechanism where the substrate influences the expression of the enzyme heparanase.
  • Understanding this regulation offers potential therapeutic targets for diseases involving heparanase activity.