Role of mechanotransduction mediated by YAP/TAZ in the treatment of neurogenic erectile dysfunction with low-intensity pulsed ultrasound.
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| Názov: | Role of mechanotransduction mediated by YAP/TAZ in the treatment of neurogenic erectile dysfunction with low-intensity pulsed ultrasound. |
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| Autori: | Liu Y; Department of Urology, The Affiliated Hospital of Changchun University of Chinese Medicine, Changchun, China., Pan XY; Department of Urology, The Affiliated Hospital of Changchun University of Chinese Medicine, Changchun, China., Zhang XX; Department of Urology, The Affiliated Hospital of Changchun University of Chinese Medicine, Changchun, China., Sun JL; Department of Urology, The Affiliated Hospital of Changchun University of Chinese Medicine, Changchun, China., Mao YH; Department of Urology, The Affiliated Hospital of Changchun University of Chinese Medicine, Changchun, China., Yang Y; Department of Urology, The Affiliated Hospital of Changchun University of Chinese Medicine, Changchun, China., Wei ZT; Department of Urology, The Affiliated Hospital of Changchun University of Chinese Medicine, Changchun, China. |
| Zdroj: | Andrology [Andrology] 2023 Oct; Vol. 11 (7), pp. 1514-1527. Date of Electronic Publication: 2023 Apr 27. |
| Spôsob vydávania: | Journal Article; Research Support, Non-U.S. Gov't |
| Jazyk: | English |
| Informácie o časopise: | Publisher: Wiley-Blackwell Country of Publication: England NLM ID: 101585129 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2047-2927 (Electronic) Linking ISSN: 20472919 NLM ISO Abbreviation: Andrology Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Oxford : Wiley-Blackwell, 2013- |
| Výrazy zo slovníka MeSH: | Erectile Dysfunction* , Mechanotransduction, Cellular* , Trauma, Nervous System*/pathology, Animals ; Male ; Mice ; Rats ; Disease Models, Animal ; Penile Erection ; Penis/pathology ; Protein Serine-Threonine Kinases ; Rats, Sprague-Dawley ; Ultrasonic Waves |
| Abstrakt: | Background: Erectile 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. Objective: The 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 Methods: Forty-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. Results: Compared 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 Conclusion: LIPUS 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. (© 2023 The Authors. Andrology published by Wiley Periodicals LLC on behalf of American Society of Andrology and European Academy of Andrology.) |
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| Contributed Indexing: | Keywords: YAP/TAZ signaling pathway; biomechanics; erectile dysfunction; low-intensity pulsed ultrasound; nerve injury |
| Substance Nomenclature: | EC 2.7.11.1 (Protein Serine-Threonine Kinases) |
| Entry Date(s): | Date Created: 20230412 Date Completed: 20231107 Latest Revision: 20231107 |
| Update Code: | 20250114 |
| DOI: | 10.1111/andr.13438 |
| PMID: | 37042189 |
| Databáza: | MEDLINE |
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Nájsť tento článok vo Web of Science | Abstrakt: | Background: Erectile 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.<br />Objective: The 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).<br />Materials and Methods: Forty-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.<br />Results: Compared 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).<br />Discussion and Conclusion: LIPUS 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.<br /> (© 2023 The Authors. Andrology published by Wiley Periodicals LLC on behalf of American Society of Andrology and European Academy of Andrology.) |
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| ISSN: | 2047-2927 |
| DOI: | 10.1111/andr.13438 |