Loss of Frmd5 Inhibits Jak2-Stat3 Signalling Pathway and Impairs Cell Apoptosis During Vagina Luminal Formation in

Tiantian Su1,2, Zhenbin Wang1, Yunjiao Wu1

  • 1Program for Cancer and Cell Biology, Department of Human Anatomy, Histology and Embryology, School of Basic Medical Sciences; Peking University International Cancer Institute; Peking University Health Science Center, 100191 Beijing, China.

Insights

FERM-domain protein 5 (Frmd5) is crucial for vaginal lumen development in mice. It activates the Jak2-Stat3 signaling pathway, essential for normal urinary epithelium formation and preventing infertility.

Area of Science:

  • Cell Biology
  • Developmental Biology
  • Molecular Mechanisms

Background:

  • FERM-domain protein 5 (Frmd5) is implicated in tumor progression and neurodevelopment.
  • Its role in normal cellular functions and urinary epithelium development is largely unknown.

Purpose of the Study:

  • To elucidate the molecular mechanisms of Frmd5 in normal cells.
  • To investigate the function of Frmd5 during urinary epithelium development.

Main Methods:

  • Investigated Frmd5 interaction with Jak2 and Stat3.
  • Utilized a urinary epithelium-specific Frmd5 knockout mouse model (Cdh16-Cre+; Frmd5flox/flox).
  • Analyzed gene expression of apoptotic and anti-apoptotic markers.

Main Results:

  • Frmd5 interacts with Jak2 and Stat3, enhancing complex formation and Stat3 phosphorylation.
  • Knockout of Frmd5 inactivated the Jak2-Stat3 pathway and reduced epithelial apoptosis.
  • Frmd5 deficiency led to decreased pro-apoptotic genes (Casp3, Casp8) and increased anti-apoptotic genes (Bcl2, Bcl-XL).
  • 56.7% of knockout mice failed to form vaginal lumens, exhibiting vaginal septum and infertility.

Conclusions:

  • Frmd5 is essential for activating the Jak2-Stat3 signaling pathway.
  • Frmd5 plays a critical role in vaginal lumen development in mice.
  • Dysregulation of Frmd5 impacts epithelial apoptosis and reproductive tract formation.

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