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Related Experiment Video

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Nrf2 Transcriptional Activity Governs Intestine Development.

Aleksandra Kopacz1, Damian Kloska1, Dominika Klimczyk1

  • 1Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, 30-387 Krakow, Poland.

International Journal of Molecular Sciences
|June 10, 2022
PubMed
Summary
This summary is machine-generated.

Nuclear factor erythroid 2-related factor 2 (Nrf2) transcriptional activity is crucial for proper intestinal development. Nrf2 deficiency in mice causes hindgut abnormalities during embryonic development, affecting cell proliferation and differentiation.

Keywords:
Nrf2Nrf2 transcriptional activitygestationhindgutintestine

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Area of Science:

  • Developmental Biology
  • Gastroenterology
  • Molecular Biology

Background:

  • Nrf2 transcriptional activity is vital for maintaining adult large intestinal structure.
  • Intestinal abnormalities in Nrf2-deficient mice may originate during early developmental stages.

Purpose of the Study:

  • To investigate if Nrf2-related intestinal abnormalities arise during gestational or early weaning periods.
  • To identify the embryonic origins of intestinal malformations in Nrf2-deficient mice.

Main Methods:

  • Analysis of Nrf2 transcriptional activity knockout (tKO) and wild-type mouse embryos and pups at different developmental stages (embryonic day 14.5, late embryonic, and postnatal day 4).
  • Histological examination of intestinal structure, including colon length, crypt distribution, and goblet cell morphology.
  • Assessment of mucin 2 levels and expression patterns of proliferation (Ki67) and differentiation (Notch1) factors.

Main Results:

  • Nrf2 tKO pups at postnatal day 4 exhibited significant intestinal structural changes: longer colon, altered crypts, and enlarged goblet cells with increased mucin 2.
  • These abnormalities were traceable to embryonic day 14.5, irrespective of sex.
  • Embryonic Nrf2 deficiency led to increased Nrf2 levels, aberrant Ki67 expression, and premature Notch1 downregulation, suggesting disturbed cell proliferation and differentiation.

Conclusions:

  • Nrf2 transcriptional activity is a critical regulator of embryonic intestinal formation.
  • Nrf2 influences hindgut cell proliferation and differentiation during key embryonic developmental stages.
  • Disturbed intestinal cell proliferation and differentiation, independent of sex, contribute to abnormalities in Nrf2-deficient mice.