Abstract
PurposeThere are multitudes of factors contributing to urinary incontinence (UI). Dysfunction of the urethral sphincter is one of the common variables. Fortunately, satellite cells, which have the characteristics of stem cells, exist in the striated urethral sphincter. The purpose of the study was to seek whether rHGF combined with rIGF-1 owns the ability to promote the activation, proliferation, and differentiation of satellite cells to potentially improve urinary incontinence.MethodsThe SD rats were randomly divided into four groups and injected with 10 μl rIGF-1, the concentration of which was 50 μg/ml into the urethral wall of the urethral sphincter. Meanwhile, three groups were additionally treated with 10 μl rHGF, the concentration of which was 20, 50, 100 μg/ml. The group injected only with rIGF-1 was used as a control. 30 days later, the urethral tissues were harvested and serially sectioned. Immunofluorescent staining and HE staining were used to detect the activation, proliferation, and differentiation condition of satellite cells. The real-time RT-PCR analysis was applied to explore the potential signaling pathways.ResultAnti-c-Met antibody-positive cells were discovered in the striated urethral sphincter. Positive expression of c-Met was relatively higher with the treatment of 100 μg/ml rHGF compared to other concentration of rHGF. A similar result was found in additional immunofluorescent staining. The number of newborn myofibers with central nuclei increased as the concentration of rHGF becoming higher. The mRNA expression of ERK1, ERK2 and AKT was comparatively higher with the injection of 50 μg/ml rHGF.ConclusionThere is supposed to be a synergistic effect between rHGF and rIGF-1 to promote satellite cell to activate, proliferate and differentiate into muscle cells. The urethral sphincter may be induced to renew by the injection of rHGF and rIGF-1 into the urethral wall. It can be used to develop a new therapy for UI.
Highlights
Urinary incontinence (UI) is defined as any involuntary loss of urine [1]
The c-Met protein played an important role in the proliferation of muscle cells; so, the expression level of c-Met was relatively high in newborn muscle tissue
To detect the effect of rat hepatocyte growth factor (rHGF) combined with rat insulin-like growth factor-1 (rIGF-1) on satellite cells growing, the urethral muscular tissue was stained with an antibody to c-Met
Summary
Urinary incontinence (UI) is defined as any involuntary loss of urine [1]. It is a common health problem and mainly affects all age groups of female populations as well as male populations [2, 3]. According to a population-based crosssectional study, the prevalence of female UI in Beijing was as high as 38.5%, of which stress urinary incontinence (SUI). The cause of UI is generally due to the weakness of the urethral sphincter [5]. Patients presenting with UI can choose suitable therapeutic approaches according to their actual condition [6, 7]. The current treatments have a certain effect, the most significant condition of urethral sphincter dysfunction has not yet thoroughly been addressed. Urethral sphincter insufficiency still exists commonly [8]
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