期刊
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
卷 702, 期 -, 页码 -出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.abb.2020.108674
关键词
Mechanical stress; Bladder outlet obstruction; Interleukin-6; Extracellular matrix remodeling
资金
- National Natural Science Foundation of China [81873601, 81770673, 81800667]
- 1.3.5 project for disciplines of excellence, West China Hospital, Sichuan University [ZY2016104, ZYGD18011]
This study found that IL-6 plays a crucial role in the mechanical stress-induced ECM remodeling of HBSMCs, indicating that IL-6 may play an essential role in BOO.
Extracellular matrix (ECM) remodeling is strongly associated with pathological changes induced by bladder outlet obstruction (BOO). In this study, we investigated the role of interleukin-6 (IL-6) in mechanical stretchinduced ECM remodeling of bladder smooth muscle. To construct a BOO animal model, the urethras of female Sprague?Dawley rats were partially ligated. In addition, increased hydrostatic pressure and mechanical stretching were applied to human bladder smooth muscle cells (HBSMCs) as an in vitro model. The expression of rat inflammatory genes was analyzed using DNA microarrays. We used quantitative RT-PCR (qRT-PCR) and immunohistochemical staining to detect IL-6 in the bladder smooth muscle of rats. To determine the specificity of IL-6, small interfering ribonucleic acid (siRNA) transfection and IL-6 receptor inhibitor (SC144) were applied to HBSMCs. qRT-PCR with siRNA transfection was also used to determine the specificity of downstream signaling. Moreover, western blotting was conducted to verify the expression results. In the animal model, the expression of ECM components and inflammatory genes was significantly upregulated. The expression of IL-6 was increased at both the mRNA level and the protein level in BOO rats. In vitro, hydrostatic pressure, and mechanical stretching both promoted MMP7 and MMP11 expression. Additionally, downregulation of collagen III occurred in both the hydrostatic pressure group and the mechanical stretch group. However, the expression of fibronectin exhibited opposing patterns between the hydrostatic pressure and mechanical stretch groups. The application of targeted siRNA transfection and an inhibitor (SC144) that targeted IL-6 significantly reversed the changes in MMP7 and MMP11 under mechanical stress and partially increased the expression of collagen III and fibronectin. In summary, IL-6 participated in the ECM remodeling of HBSMCs under mechanical stress, indicating that IL-6 may play an essential role in BOO.
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