The DOI matches its Crossref record; 13 of the 13 references it cites were found in a registry or an index.
YAP/TAZ Are Mechanoregulators of TGF-β-Smad Signaling and Renal Fibrogenesis
Open accessAbstract
Like many organs, the kidney stiffens after injury, a process that is increasingly recognized as an important driver of fibrogenesis. Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ) are related mechanosensory proteins that bind to Smad transcription factors, the canonical mediators of profibrotic TGF-β responses. Here, we investigated the role of YAP/TAZ in the matrix stiffness dependence of fibroblast responses to TGF-β. In contrast to growth on a stiff surface, fibroblast growth on a soft matrix led to YAP/TAZ sequestration in the cytosol and impaired TGF-β–induced Smad2/3 nuclear accumulation and transcriptional activity. YAP knockdown or treatment with verteporfin, a drug that was recently identified as a potent YAP inhibitor, elicited similar changes. Furthermore, verteporfin reduced YAP/TAZ levels and decreased the total cellular levels of Smad2/3 after TGF-β stimulation. Verteporfin treatment of mice subjected to unilateral ureteral obstruction similarly reduced YAP/TAZ levels and nuclear Smad accumulation in the kidney, and attenuated renal fibrosis. Our data suggest that organ stiffening cooperates with TGF-β to induce fibrosis in a YAP/TAZ- and Smad2/3-dependent manner. Interference with this YAP/TAZ and TGF-β/Smad crosstalk likely underlies the antifibrotic activity of verteporfin. Finally, through repurposing of a clinically used drug, we illustrate the therapeutic potential of a novel mechanointerference strategy that blocks TGF-β signaling and renal fibrogenesis.
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Cites
Role of YAP/TAZ in mechanotransduction
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A coordinated phosphorylation by Lats and CK1 regulates YAP stability through SCF β-TRCP
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Nuclear CDKs Drive Smad Transcriptional Activation and Turnover in BMP and TGF-β Pathways
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Increased stiffness of the rat liver precedes matrix deposition: implications for fibrosis
Georges, P. C., Hui, J.-J., Gombos, Z., McCormick, M. E., Wang, A. Y., Uemura, M., Mick, R., Janmey, P. A., Furth, E. E., & Wells, R. G. (2007) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00032.2007 · Cited by 577
Matrix stiffness-induced myofibroblast differentiation is mediated by intrinsic mechanotransduction
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The Hippo pathway effector YAP controls mouse hepatic stellate cell activation
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Cited by
Frangogiannis, N. G. (2021) · Cardiovascular Research · doi:10.1093/cvr/cvaa324 · Cited by 1,229
Targeting the Hippo pathway in cancer, fibrosis, wound healing and regenerative medicine
Dey, A., Varelas, X., & Guan, K.-L. (2020) · Nature Reviews Drug Discovery · doi:10.1038/s41573-020-0070-z · Cited by 860
Unilateral Ureteral Obstruction as a Model to Investigate Fibrosis-Attenuating Treatments
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Mechanical stiffness controls dendritic cell metabolism and function
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The Role of Myofibroblasts in Physiological and Pathological Tissue Repair
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Metadata
- Authors
- Szeto, S. G., Narimatsu, M., Lu, M., He, X., Sidiqi, A. M., Tolosa, M. F., Chan, L., De Freitas, K., Bialik, J. F., Majumder, S., Boo, S., Hinz, B., Dan, Q., Advani, A., John, R., Wrana, J. L., Kapus, A., & Yuen, D. A.
- Venue
- Journal of the American Society of Nephrology
- Published
- 2016-03-09
- Volume
- 27
- Issue
- 10
- Pages
- 3117-3128
- ISSN
- 1046-6673 (ISSN-L)
- 1533-3450
- OpenAlex
- W2295717665
- Cited by
- 462
- References
- 13
- FWCI
- 19.17
- Type
- journal article
- Language
- en
- Open access
- green
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- Szeto, S. G., Narimatsu, M., Lu, M., He, X., Sidiqi, A. M., Tolosa, M. F., Chan, L., De Freitas, K., Bialik, J. F., Majumder, S., Boo, S., Hinz, B., Dan, Q., Advani, A., John, R., Wrana, J. L., Kapus, A., & Yuen, D. A. (2016). YAP/TAZ Are Mechanoregulators of TGF-β-Smad Signaling and Renal Fibrogenesis. Journal of the American Society of Nephrology. https://doi.org/10.1681/asn.2015050499
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
