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Related Concept Videos

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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The liver is an important organ in vertebrates that plays an essential role in metabolism. It is also responsible for storing and redistributing nutrients such as carbohydrates, fats, and vitamins in the body. Additionally, the liver releases bile salts which are critical for digesting food and eliminating toxic metabolites from the body.
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Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
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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.
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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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Cell Specific Gene Expression

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Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...
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Hedgehog Signaling: Implications in Liver Pathophysiology.

Rajesh Kumar Dutta1, JiHye Jun1, Kuo Du1

  • 1Department of Medicine, Duke University, Durham, North Carolina.

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The Hedgehog signaling pathway is crucial for liver health, regulating stem cells and tissue repair. Precise control of this pathway in adult liver cells is essential to prevent diseases like cirrhosis and cancer.

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Area of Science:

  • Molecular Biology
  • Hepatology
  • Developmental Biology

Background:

  • The Hedgehog signaling pathway is a critical morphogenic pathway active during development.
  • In adult tissues, its activity is typically confined to stem and stromal cells, maintaining tissue homeostasis.
  • Aberrant Hedgehog signaling is implicated in various cancers and tissue repair processes.

Approach:

  • This review summarizes current knowledge on the Hedgehog pathway's role in liver homeostasis and disease.
  • It examines the pathway's function in normal liver physiology and its dysregulation in pathological conditions.
  • Recent findings on hepatocyte-specific Hedgehog signaling are discussed.

Key Points:

  • Sustained Hedgehog signaling in liver stromal cells drives cirrhosis pathogenesis.
  • Disruption of Hedgehog signaling in hepatocytes dysregulates metabolism and promotes lipotoxicity, insulin resistance, and senescence.
  • Hepatocyte Hedgehog deficiency can induce inflammatory and fibrogenic responses in cholangiocytes and stromal cells, exacerbating fibrosis.

Conclusions:

  • Precise regulation of Hedgehog signaling in adult liver cells is vital for maintaining liver health.
  • Understanding this pathway's complex roles offers potential therapeutic targets for liver diseases.
  • Further research is needed to fully elucidate the consequences of Hedgehog pathway dysregulation in hepatocytes.