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Related Concept Videos

Anatomy of the Genitourinary System II: Bladder and Urethra01:19

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The lower urinary system consists of the urinary bladder and urethra, which are essential in storing and expelling urine from the body. Together with the internal and external sphincters, these structures work together to regulate urination effectively.Anatomy of the BladderThe urinary bladder is a muscular, stretchable organ behind the pubic bone and in front of the rectum. In females, the bladder is positioned anterior to the vagina and inferior to the uterus, while in males, it is located...
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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.
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The urinary bladder is a hollow, muscular sac that temporarily stores urine before it is expelled from the body. It can hold approximately 600 mL of urine prior to micturition. The bladder is retroperitoneal and located behind the pubic symphysis in the pelvic floor.
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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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Urination, or micturition involves the coordination of the bladder's detrusor muscle and two sphincters to ensure controlled bladder emptying.
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Notch controls urothelial integrity in the mouse bladder.

Varvara Paraskevopoulou1,2, Vangelis Bonis1, Vasilis S Dionellis3,4

  • 1Biomedical Research Foundation of the Academy of Athens, Athens, Greece.

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|February 14, 2020
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Summary

Notch signaling is crucial for bladder health, acting as a tumor suppressor. Its inactivation causes bladder dysfunction and mimics interstitial cystitis/bladder pain syndrome (IC/BPS) in mice.

Keywords:
Cell BiologyExtracellular matrixIntegrins

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Area of Science:

  • Urology
  • Cell Biology
  • Molecular Biology

Background:

  • The Notch signaling pathway regulates cell communication, differentiation, and proliferation.
  • Notch acts as a tumor suppressor in mouse bladders, and its pathway components are mutated in human bladder cancer.

Purpose of the Study:

  • To investigate the role of Notch signaling in maintaining urinary bladder homeostasis.
  • To explore the link between Notch pathway activity and interstitial cystitis/bladder pain syndrome (IC/BPS).

Main Methods:

  • Genetic inactivation of Notch in mouse models.
  • Molecular profiling of mouse bladder tissue.
  • Comparison with human IC/BPS patient tissue.

Main Results:

  • Notch inactivation led to impaired cell-cell and cell-extracellular matrix interactions, structural defects, inflammation, and a leaky urine-blood barrier.
  • Ailing mouse bladders showed molecular similarities to IC/BPS patient tissue with low Notch activity.
  • Restoring Notch pathway activity reconstituted urothelial integrity.

Conclusions:

  • Notch signaling plays a critical role in bladder homeostasis, regulating urothelial integrity and microenvironment interactions.
  • Dysfunctional Notch signaling is implicated in IC/BPS pathogenesis.
  • Further research into α4 integrin's role in urothelial homeostasis is warranted.