ArticleNature communications2023
The role of mechano-regulated YAP/TAZ in erectile dysfunction.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed.
- Hydrogels: current biomedical applications and future directions.Molecular biomedicine · 2026Review
- A comprehensive landscape of mechanical stress-mediated lipid metabolism in human cavernous fibroblasts.Communications biology · 2026Article
- LIPUS promotes stem leydig cells proliferation by up-regulating Wnt5a expression and delays male aging.Scientific reports · 2026Article
- Mechanosensor YAP orchestrates human neural rosette morphogenesis via TEAD4-LEF1 transcriptional nexus.Science China. Life sciences · 2026Article
- Quercetin alleviates radiation-induced erectile dysfunction by modulating oxidative stress and apoptosis through the Nrf2/HO-1 pathway.European journal of medical research · 2026Article
- Improving erectile function in diabetic male mice by rescuing depalmitoylated FBP1 to reduce cavernosal lactate.Nature communications · 2026Article
- Benign Uroandrological Ecosystem: A Thorough Overview from Single-Cell and Spatial Transcriptomics.Research (Washington, D.C.) · 2026Review
- PABPC3 drives ovarian cancer metastasis and drug sensitivity by downregulating CLDN1 expression.Cell death & disease · 2025Article
- Mechanotransduction in Shaping Immunity: Pathways, Crosstalk, and Pathophysiological Relevance.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Yes-Associated Protein Promotes Endothelial-Mesenchymal Transition to Mediate Diabetes Mellitus Erectile Dysfunction by Phosphorylating Smad3.The world journal of men's health · 2025Article
- Blocking TSP1 Ameliorates Diabetes Mellitus-Induced Erectile Dysfunction by Inhibiting the TGF-β/SMAD Pathway.The world journal of men's health · 2025Article
- Autophagy induced by mechanical stress sensitizes cells to ferroptosis by NCOA4-FTH1 axis.Autophagy · 2025Article
- Deciphering mechanical cues in the microenvironment: from non-malignant settings to tumor progression.Biomarker research · 2025Review
- Associations between metabolic syndrome and erectile dysfunction: evidence from the NHANES 2001-2004.Frontiers in public health · 2025Article
- Article
- Metabolism of cancer cells and immune cells in the initiation, progression, and metastasis of cancer.Theranostics · 2025Review
- Article
- Magnetic soft microrobots for erectile dysfunction therapy.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- The correlation between premature ejaculation and a high incidence of erectile dysfunction and its research progress: a narrative review.Translational andrology and urology · 2024Review
- Mechano-YAP/TAZ-regulated smooth muscle cells are an important source of Wnt signalling for gut regeneration.Clinical and translational medicine · 2024Article
Corrections and comments
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Authors and funding
18 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Phosphodiesterase type 5 inhibitors (PDE5is) constitute the primary therapeutic option for treating erectile dysfunction (ED). Nevertheless, a substantial proportion of patients, approximately 30%, do not respond to PDE5i treatment. Therefore, new treatment methods are needed. In this study, we identified a pathway that contributes to male erectile function. We show that mechano-regulated YAP/TAZ signaling in smooth muscle cells (SMCs) upregulates adrenomedullin transcription, which relaxed the SMCs to maintain erection. Using single-nucleus RNA sequencing, we investigated how penile erection stretches the SMCs, inducing YAP/TAZ activity. Subsequently, we demonstrate that YAP/TAZ plays a role in erectile function and penile rehabilitation, using genetic lesions and various animal models. This mechanism relies on direct transcriptional regulation of adrenomedullin by YAP/TAZ, which in turn modulates penile smooth muscle contraction. Importantly, conventional PDE5i, which targets NO-cGMP signaling, does not promote erectile function in YAP/TAZ-deficient ED model mice. In contrast, by activating the YAP/TAZ-adrenomedullin cascade, mechanostimulation improves erectile function in PDE5i nonrespondent ED model rats and mice. Furthermore, using clinical retrospective observational data, we found that mechanostimulation significantly promotes erectile function in patients irrespective of PDE5i use. Our studies lay the groundwork for exploring the mechano-YAP/TAZ-adrenomedullin axis as a potential target in the treatment of ED.
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