rHGF interacts with rIGF-1 to activate the satellite cells in the striated urethral sphincter in rats: a promising treatment for urinary incontinence?

PURPOSE: There 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. METHODS: The 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. RESULT: Anti-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. CONCLUSION: There 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.