Details

Autor(en) / Beteiligte

• Uemura, Ryo
• Tachibana, Daisuke
• Shiota, Masayuki
• Yoshida, Kayo
• Kitada, Kohei
• Hamuro, Akihiro
• Misugi, Takuya
• Koyama, Masayasu

Titel

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

Ist Teil von

• International Urogynecology Journal, 2021-11, Vol.32 (11), p.2993-2999

Ort / Verlag

Cham: Springer International Publishing

Erscheinungsjahr

2021

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.