Effect of integrin β1 in the treatment of stress urinary incontinence by electrical stimulation

Abstract

The aim of the present study was to investigate the protective effect of integrin β1 in the treatment of stress urinary incontinence (SUI) by electrical stimulation, and the underlying mechanisms by which electrical stimulation regulates the collagen metabolism of female vaginal wall fibroblasts (FVWFs). FVWFs obtained from the vaginal wall tissue of patients with (Ingelman-Sundberg scale; grade II, n=8; grade III, n=10) or without (n=8) SUI during gynecological operations were isolated by enzymatic digestion and subsequently identified by immunocytochemistry. Following this, cultured FVWFs were treated with an inhibitor of integrin β1, recombinant human integrin β1 and electrical stimulation (100 mv/mm, 2 h, 20 Hz), followed by total mRNA and protein extraction. mRNA and protein expression levels of integrin β1, transforming growth factor (TGF)-β1 and collagen (COL) I and III in FVWFs were quantified by reverse transcription-quantitative PCR (RT-qPCR) and western blot analysis respectively. Integrin β1, TGF-β1 and COL I and III expression levels were decreased in patients with SUI compared with healthy controls, and the grade III group had lower levels than the grade II group. Following electrical stimulation treatment, the expression levels of TGF-β1, COL I and III were enhanced in the grade II group, but not in the grade III group. Nevertheless, the inhibitor of integrin β1 reduced the protective effect of electrical stimulation in the grade II group. In addition, electrical stimulation combined with recombinant human integrin β1 could also protect cells from SUI in the grade III group. The present study provides evidence for the increased degradation of the extracellular matrix and integrin β1 in the vaginal wall tissues of patients with SUI, and the protective effect of electrical stimulation against SUI via integrin β1. These results provide a novel mechanism for the treatment of SUI using electrical stimulation.

Molecular Processes in Stress Urinary Incontinence: A Systematic Review of Human and Animal Studies

“…All studies included women and female animals only. Of the human studies, SUI alone was investigated in 52 human studies [ 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 ], and SUI with the co-occurrence of POP in 23 studies [ 62 , 72 , 73 , 74 ...…”

Monophasic Pulsed Current Stimulation of Duty Cycle 10% Promotes Differentiation of Human Dermal Fibroblasts into Myofibroblasts

“…Moreover, it is not clear which cell sensor received ES to promote TGF-β1 and α-SMA expression. TGF-β1-mediated signals are enhanced via integrin β1, which is a cell surface receptor 24 )…”

Application of estrogen for the treatment of stress urinary incontinence in mice

“…It is a complex long-chain protein mixture, composed of collagen, elastin, and proteoglycan 18 . Previous studies have con rmed that ECM remodeling is an important association in the pathogenesis of SUI 19 . It has been found that estrogen affects the transcription and expression of collagen, which are the main component of ECM 20 .…”

“…Meanwhile, reports on the remodeling of ECM caused by estrogen are not systematic. Therefore, in this article, according to our previous experience 25 , we constructed the animal model of stress urinary incontinence by vaginal dilation, and correspondingly, we constructed the mechanical injury model of L929 broblasts 26 . We have described the application of topical estrogen to treat SUI from the animal and cellular level to investigate the reasons affecting the e cacy of topical estrogen for SUI, the mechanism by which estrogen affects the expression of ECM, and then pave the way for the mechanism of treatment effects.…”