Yes-Associated Protein Promotes Endothelial-Mesenchymal Transition to Mediate Diabetes Mellitus Erectile Dysfunction by Phosphorylating Smad3
Purpose: The main objective of this study is to elucidate the role of endothelial-mesenchymal transition (EndMT) regulated by yes-associated protein (YAP) on diabetes mellitus erectile dysfunction (DMED). Materials and Methods: High concentrations of glucose and palmitic acid (HGP) culturing simul...
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Korean Society for Sexual Medicine and Andrology
2025-07-01
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| Series: | The World Journal of Men's Health |
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| author | Ming Xiao Xiaoli Tan Huanqin Zeng Biao Liu Xiaopeng Tang Yanghua Xu Yinghao Yin Jiarong Xu Zhitao Han Zitaiyu Li Yuxin Tang Liangyu Zhao |
| author_facet | Ming Xiao Xiaoli Tan Huanqin Zeng Biao Liu Xiaopeng Tang Yanghua Xu Yinghao Yin Jiarong Xu Zhitao Han Zitaiyu Li Yuxin Tang Liangyu Zhao |
| author_sort | Ming Xiao |
| collection | DOAJ |
| description | Purpose: The main objective of this study is to elucidate the role of endothelial-mesenchymal transition (EndMT) regulated by
yes-associated protein (YAP) on diabetes mellitus erectile dysfunction (DMED).
Materials and Methods: High concentrations of glucose and palmitic acid (HGP) culturing simulated a diabetic condition in
vitro. Cell proliferation, migration, tube formation, and marker gene changes of rat cavernous endothelial cells (RCECs) were
measured after YAP overexpression or knockdown. Erectile function and histological outcomes were evaluated in vivo.
Results: Nuclear YAP in RCECs was significantly increased after pretreatment with HGP. YAP overexpression enhanced the cell
proliferation (0.236±0.004 vs. 0.148±0.008, p<0.001), migration (1.908±0.099 vs. 1.000±0.116, p<0.001), and tube formation
(290.6±10.96 and 21,440.3±762.9 vs. 175.0±24.82 and 13,538.6±1,819.0, p<0.001) compared to the control group.
Moreover, the ratios of intracavernous pressure (ICP) to mean arterial pressure (MAP) (0.642±0.051 vs. 0.850±0.070, p<0.05),
and smooth muscle to collagen (0.155±0.010 vs. 0.274±0.023, p<0.01) were decreased in rats with YAP overexpression. The
effects of HGP on CD31, eNOS, CD34, VE-cadherin, vimentin, α-SMA, and p-Smad3 expression were abrogated by inhibiting
YAP in RCECs. YAP knockdown also restored the ICP/MAP (0.597±0.019 vs. 0.346±0.033, p<0.01), smooth muscle/collagen
(0.13±0.010 vs. 0.08±0.026, p<0.05) and p-Smad3/Smad3 (1.61±0.291 vs. 3.26±0.332, p<0.01) ratios in type 2 diabetic rats.
Conclusions: YAP promotes EndMT to impair erectile function in type 2 diabetic rats by phosphorylating Smad3, providing a
new strategy for treating DMED. |
| format | Article |
| id | doaj-art-82e67c7ed68c47a7a852c7cc028c44ff |
| institution | DOAJ |
| issn | 2287-4208 2287-4690 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Korean Society for Sexual Medicine and Andrology |
| record_format | Article |
| series | The World Journal of Men's Health |
| spelling | doaj-art-82e67c7ed68c47a7a852c7cc028c44ff2025-08-20T03:16:31ZengKorean Society for Sexual Medicine and AndrologyThe World Journal of Men's Health2287-42082287-46902025-07-0143368670110.5534/wjmh.240126Yes-Associated Protein Promotes Endothelial-Mesenchymal Transition to Mediate Diabetes Mellitus Erectile Dysfunction by Phosphorylating Smad3Ming Xiao0https://orcid.org/0000-0003-3576-3617Xiaoli Tan1https://orcid.org/0000-0002-9132-3205Huanqin Zeng2https://orcid.org/0009-0004-1811-1857Biao Liu3https://orcid.org/0000-0002-9475-0704Xiaopeng Tang4https://orcid.org/0009-0000-6282-8127Yanghua Xu5https://orcid.org/0000-0002-9140-2069Yinghao Yin6https://orcid.org/0000-0001-9862-9082Jiarong Xu7https://orcid.org/0000-0003-0344-8890Zhitao Han8https://orcid.org/0009-0004-3616-8689Zitaiyu Li9https://orcid.org/0000-0003-0805-8816Yuxin Tang10https://orcid.org/0000-0003-4694-558XLiangyu Zhao11https://orcid.org/0000-0003-1070-3466Department of Urology, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, ChinaDepartment of Urology, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, ChinaDepartment of Urology, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, ChinaDepartment of Urology, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, ChinaDepartment of Biological Sciences, The University of Edinburgh, Edinburgh, Scotland, UKDepartment of Urology, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, ChinaDepartment of Urology, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, ChinaDepartment of Urology, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, ChinaDepartment of Urology, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, ChinaDepartment of Urology, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, ChinaDepartment of Urology, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, ChinaDepartment of Urology, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, ChinaPurpose: The main objective of this study is to elucidate the role of endothelial-mesenchymal transition (EndMT) regulated by yes-associated protein (YAP) on diabetes mellitus erectile dysfunction (DMED). Materials and Methods: High concentrations of glucose and palmitic acid (HGP) culturing simulated a diabetic condition in vitro. Cell proliferation, migration, tube formation, and marker gene changes of rat cavernous endothelial cells (RCECs) were measured after YAP overexpression or knockdown. Erectile function and histological outcomes were evaluated in vivo. Results: Nuclear YAP in RCECs was significantly increased after pretreatment with HGP. YAP overexpression enhanced the cell proliferation (0.236±0.004 vs. 0.148±0.008, p<0.001), migration (1.908±0.099 vs. 1.000±0.116, p<0.001), and tube formation (290.6±10.96 and 21,440.3±762.9 vs. 175.0±24.82 and 13,538.6±1,819.0, p<0.001) compared to the control group. Moreover, the ratios of intracavernous pressure (ICP) to mean arterial pressure (MAP) (0.642±0.051 vs. 0.850±0.070, p<0.05), and smooth muscle to collagen (0.155±0.010 vs. 0.274±0.023, p<0.01) were decreased in rats with YAP overexpression. The effects of HGP on CD31, eNOS, CD34, VE-cadherin, vimentin, α-SMA, and p-Smad3 expression were abrogated by inhibiting YAP in RCECs. YAP knockdown also restored the ICP/MAP (0.597±0.019 vs. 0.346±0.033, p<0.01), smooth muscle/collagen (0.13±0.010 vs. 0.08±0.026, p<0.05) and p-Smad3/Smad3 (1.61±0.291 vs. 3.26±0.332, p<0.01) ratios in type 2 diabetic rats. Conclusions: YAP promotes EndMT to impair erectile function in type 2 diabetic rats by phosphorylating Smad3, providing a new strategy for treating DMED.diabetes mellitusendothelial-mesenchymal transitionerectile dysfunctionsmad family member 3yes-associated protein |
| spellingShingle | Ming Xiao Xiaoli Tan Huanqin Zeng Biao Liu Xiaopeng Tang Yanghua Xu Yinghao Yin Jiarong Xu Zhitao Han Zitaiyu Li Yuxin Tang Liangyu Zhao Yes-Associated Protein Promotes Endothelial-Mesenchymal Transition to Mediate Diabetes Mellitus Erectile Dysfunction by Phosphorylating Smad3 The World Journal of Men's Health diabetes mellitus endothelial-mesenchymal transition erectile dysfunction smad family member 3 yes-associated protein |
| title | Yes-Associated Protein Promotes Endothelial-Mesenchymal Transition to Mediate Diabetes Mellitus Erectile Dysfunction by Phosphorylating Smad3 |
| title_full | Yes-Associated Protein Promotes Endothelial-Mesenchymal Transition to Mediate Diabetes Mellitus Erectile Dysfunction by Phosphorylating Smad3 |
| title_fullStr | Yes-Associated Protein Promotes Endothelial-Mesenchymal Transition to Mediate Diabetes Mellitus Erectile Dysfunction by Phosphorylating Smad3 |
| title_full_unstemmed | Yes-Associated Protein Promotes Endothelial-Mesenchymal Transition to Mediate Diabetes Mellitus Erectile Dysfunction by Phosphorylating Smad3 |
| title_short | Yes-Associated Protein Promotes Endothelial-Mesenchymal Transition to Mediate Diabetes Mellitus Erectile Dysfunction by Phosphorylating Smad3 |
| title_sort | yes associated protein promotes endothelial mesenchymal transition to mediate diabetes mellitus erectile dysfunction by phosphorylating smad3 |
| topic | diabetes mellitus endothelial-mesenchymal transition erectile dysfunction smad family member 3 yes-associated protein |
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