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- Title
Upregulation of PTK7 and β-catenin after vaginal mechanical dilatation: an examination of fibulin-5 knockout mice.
- Authors
Uemura, Ryo; Tachibana, Daisuke; Shiota, Masayuki; Yoshida, Kayo; Kitada, Kohei; Hamuro, Akihiro; Misugi, Takuya; Koyama, Masayasu
- Abstract
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.
- Subjects
KNOCKOUT mice; PROTEIN-tyrosine kinases; PELVIC organ prolapse; LIQUID chromatography-mass spectrometry; MASS spectrometry
- Publication
International Urogynecology Journal, 2021, Vol 32, Issue 11, p2993
- ISSN
0937-3462
- Publication type
Article
- DOI
10.1007/s00192-021-04693-2