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 us...

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Bibliographic Details
Published in:International Urogynecology Journal 2021-11, Vol.32 (11), p.2993-2999
Main Authors: Uemura, Ryo, Tachibana, Daisuke, Shiota, Masayuki, Yoshida, Kayo, Kitada, Kohei, Hamuro, Akihiro, Misugi, Takuya, Koyama, Masayasu
Format: Article
Language:English
Subjects:
Animals
beta Catenin - metabolism
Calcium-Binding Proteins - genetics
Chromatography, Liquid
Dilatation
Extracellular Matrix Proteins - genetics
Female
Gynecology
Medicine
Medicine & Public Health
Mice
Mice, Knockout
Original Article
Proteins
Receptor Protein-Tyrosine Kinases - metabolism
Rodents
Stress, Mechanical
Tandem Mass Spectrometry
Up-Regulation
Urology
Vagina
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Summary: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.
ISSN:0937-3462
1433-3023
DOI:10.1007/s00192-021-04693-2