Nampt promotes fibroblast extracellular matrix degradation in stress urinary incontinence by inhibiting autophagy. Issue 1 (1st January 2022)

• Record Type: Journal Article
• Authors: Zhang, Hui; Wang, Lu; Xiang, Yuancui; Wang, Yali; Li, Hongjuan
• Is Part Of: Bioengineered. Volume 13:Issue 1(2022)
• Page Start: 481
• Page End: 495
• Publication Date: 2022-01-01
• Subjects: Stress urinary incontinence -- extracellular matrix metabolism -- autophagy -- Nampt -- fibroblast; Biomedical engineering -- Periodicals; Biotechnology -- Periodicals; Microbiology -- Periodicals; 660.6
• DOI: 10.1080/21655979.2021.2009417
• Languages: English
• ISSNs: 2165-5987

Abstract

ABSTRACT: Stress urinary incontinence (SUI) is defined as involuntary urinary leakage happening in exertion. Nicotinamide phosphoribosyltransferase (Nampt) is seldom researched in the pathogenesis of SUI. Accordingly, the current study set out to elucidate the role of Nampt in SUI progression. Firstly, we determined Nampt expression patterns in SUI patients and rat models. In addition, fibroblasts were obtained from the anterior vaginal wall tissues of non-SUI patients and subjected to treatment with different concentrations of interleukin-1β (IL-1β), followed by quantification of Nampt expressions in fibroblasts. Subsequently, an appropriate concentration of IL-1β was selected to treat anterior vaginal wall fibroblasts. Nampt was further silenced in IL-1β-treated fibroblasts to assess the role of Nampt in autophagy and extracellular matrix (ECM) degradation. Lastly, functional rescue assays were carried out to inhibit autophagy and evaluate the role of autophagy in the mechanism of Nampt modulating IL-1β-treated fibroblast ECM degradation. It was found that Nampt was highly-expressed in SUI patients and rat models and IL-1β-treated fibroblasts. On the other hand, Nampt silencing was found to suppress ECM degradation and promote SUI fibroblast autophagy. Additionally, inhibition of autophagy attenuated the inhibitory effects of Nampt silencing on SUI fibroblast ECM degradation. Collectively, our findings revealed that Nampt was over-expressed in SUI, whereas Nampt silencing enhanced SUI fibroblast autophagy, and thereby inhibited ECM degradation.