Upregulation of PTK7 and β-catenin after vaginal mechanical dilatation: an examination of fibulin-5 knockout mice.

INTRODUCTION AND HYPOTHESIS

Pelvic organ prolapse (POP) in women is associated with deficiency of elastic fibers, and fibulin-5 is known to be a critical protein in the synthesis of elastin. The purpose of this study is to investigate the related pathway for the synthesis of elastin via fibulin-5 using fibulin-5 knockout mice.

METHODS

Fibulin-5 knockout mice were generated using the CRISPR/Cas9 system, and vaginal dilatation was used to mimic vaginal delivery. We divided the mice into three groups: Fbln5 mice immediately after dilatation (Fbln5 day0), Fbln5 mice 3 days after dilatation (Fbln5 day3) and Fbln5 mice 3 days after dilatation (Fbln5 day3). Proteins related to elastogenesis in the vaginal wall were measured by liquid chromatography mass spectrometry (LC-MS/MS) analysis, and differences in the expression of these proteins between the Fbln5 mice and the Fbln5 mice were analyzed using western blotting.

RESULTS

In the LC-MS/MS analysis, protein tyrosine kinase 7 (PTK7) was not detected in the Fbln5 day3 group, although the expression increased by > 1.5 times between the Fbln5 day0 and day3 groups. PTK7 and β-catenin are known to act in the Wnt/β-catenin pathway, and both were upregulated after dilatation in the Fbln5 mice, though not in the Fbln5 mice.

CONCLUSION

Our findings suggest that these proteins are involved in elastogenesis via fibulin-5, and the impairment of these proteins might be the underlying cause of POP manifestation.