Role of mechanotransduction mediated by YAP/TAZ in the treatment of neurogenic erectile dysfunction with low-intensity pulsed ultrasound

被引:9
作者
Liu, Yang [1 ]
Pan, Xiao-ying [1 ]
Zhang, Xiang-xiang [1 ]
Sun, Ji-lei [1 ]
Mao, Yin-hui [1 ]
Yang, Yong [1 ,2 ]
Wei, Zhi-tao [1 ,2 ]
机构
[1] Changchun Univ Chinese Med, Dept Urol, Affiliated Hosp, Changchun, Peoples R China
[2] Changchun Univ Chinese Med, Dept Urol, Affiliated Hosp, Changchun 130021, Peoples R China
关键词
biomechanics; erectile dysfunction; low-intensity pulsed ultrasound; nerve injury; YAP; TAZ signaling pathway; NERVE INJURY; PATHWAY; YAP;
D O I
10.1111/andr.13438
中图分类号
R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
摘要
BackgroundErectile dysfunction (ED) and weakness of the penis are processes related to hemodynamic alteration. Low-intensity pulsed ultrasound (LIPUS), as a new mechanical modality for the treatment of ED, deserves to be explored in depth for the biomechanical mechanisms it exerts. ObjectiveThe aim of this study was to explore the role of YAP/TAZ-mediated mechanotransduction in mechanical therapy for the treatment of neurogenic erectile dysfunction (NED). Materials and methodsForty-two male SD rats (12 w old) were randomly divided into sham-operated (n = 14), bilateral cavernous nerve injury (BCNI, n = 14), and LIPUS-treated (n = 14) groups. Intracavernosal pressure/mean arterial pressure (ICP/MAP) was measured 14 and 28 days after treatment. Penile tissue specimens were collected for pathological examination, and the changes in YAP, TAZ, connective tissue growth factor (CTGF), CYR61, LATS1, and p38 mitogen-activated protein kinase expression levels were assessed by Western blot, real-time quantitative polymerase chain reaction (RT-qPCR) and immunological staining. ResultsCompared with BCNI, LIPUS significantly improved ICP/MAP levels and enhanced histopathological changes. The penile expression levels of YAP, TAZ, CTGF, and CYR61 were significantly downregulated in the BCNI group (p < 0.01), and LIPUS upregulated the expression levels of these proteins (p < 0.05). The expression levels of p-LATS1 and LATS1 were not significantly different among the groups (p > 0.05). Interestingly, the expression level of p-p38/p38 significantly increased in BCNI rats (p < 0.05), which was reversed by LIPUS treatment (p < 0.05). However, the p38 inhibitor SB203580 did not change the expression of YAP/TAZ in rat primary smooth muscle cells or mouse MOVAS cells (p > 0.05). Discussion and conclusionLIPUS can effectively improve penile erectile function in NED rats. The underlying mechanism may be related to the regulation of YAP/TAZ-mediated mechanotransduction. However, the upstream regulatory signal may differ from the classical Hippo pathway.
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页码:1514 / 1527
页数:14
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