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

FRMD5, FERM-domain protein 5, has been reported to be associated with tumors progession and neurodevelopment, however its molecular mechanisms in normal cells and its functions during urinary epithelium development remain unknown. In this study, we identified that Frmd5 interacts with Jak2 and Stat3, leading to the enhanced Jak2/Stat3 complex formation and subsquently promoting phosphorylation of Stat3. In a urinary epithelium specific knockout of Frmd5 mouse, Jak2-Stat3 signaling pathway was significantly inactivated and apoptosis of epithelium was significantly downregulated compared with Cdh16-Cre-; Frmd5(flox/flox) control mouse. In Cdh16-Cre+; Frmd5(flox/flox) vaginal epithelium pro-apoptotic genes (Casp3, Casp8) was decreased and anti-apoptotic genes (Bcl2, Bcl-XL) was increased compared with Cdh16-Cre-; Frmd5(flox/flox) vaginal epithelium. A total of 56.7% Cdh16-Cre+; Frmd5(flox/flox) mice failed to form vaginal lumen and developed longitudinal vaginal septum coupled with infertility in these mice. In summary, we demonstrated that Frmd5 is essential for activation of Jak2-Stat3 signaling pathway and is required for vaginal lumen development in mice.