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Erschienen in:
27.01.2020 | Original Article
Effects of mechanical trauma on the differentiation and ArfGAP3 expression of C2C12 myoblast and mouse levator ani muscle
Erschienen in: International Urogynecology Journal | Ausgabe 9/2020
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Introduction and hypothesis
Severe mechanical injury or inadequate repair of the levator ani muscle (LAM) is a key contributor to the development of pelvic floor dysfunction (PFD). We explored the effects of mechanical stress on myoblasts and LAM at the cellular and animal level and the possible mechanism of PFD induced by mechanical trauma.
Methods
A C2C12 cell mechanical injury model was established with a four-point bending device, and a LAM injury mouse model was established via vaginal distention and distal traction, a common way of simulating the birth injury. The cells were divided into control, 1333 μ strain for 4-h cyclic mechanical strain (CMS), 1333 μ strain for 8-h CMS, and 5333 μ strain for 4-h CMS groups. Mice were divided into control and injury groups. After treatment, mitochondrial membrane potential (ΔΨm), reactive oxygen species (ROS) levels, indicators of oxidative damage, cell apoptosis, muscle and cell morphology, cell differentiation, and expression of adenosine diphosphate (ADP)-ribosylation factor GTPase activating protein 3 (ArfGAP3) were detected.
Results
5333 μ strain for 4-h CMS loading could induce myoblast injury with a reduction of ΔΨm, increased ROS levels, aggravation of oxidative damage-associated proteins NADPH oxidase 2 (NOX2) and xanthine oxidase (XO), and an increased apoptosis rate of C2C12 cells. At the same time, the injury CMS loading can promote the differentiation of myoblasts and increase the expression of ArfGAP3, a factor regulating intracellular transport. Mechanical trauma could also lead to the oxidative damage of LAM, indicated by 8-hydroxy-2′-deoxyguanosine(8-OHdG), NOX2 and XO protein accumulation, and increase the expression of ArfGAP3 in LAM.
Conclusions
Oxidative stress caused by mechanical trauma induces dysfunction and damage repairing of LAM and C2C12 myoblast, and ArfGAP3 may promote the repairing process.