The DOI matches its Crossref record; 52 of the 52 references it cites were found in a registry or an index.
Klotho Inhibits Transforming Growth Factor-β1 (TGF-β1) Signaling and Suppresses Renal Fibrosis and Cancer Metastasis in Mice
Open accessAbstract
Fibrosis is a pathological process characterized by infiltration and proliferation of mesenchymal cells in interstitial space. A substantial portion of these cells is derived from residing non-epithelial and/or epithelial cells that have acquired the ability to migrate and proliferate. The mesenchymal transition is also observed in cancer cells to confer the ability to metastasize. Here, we show that renal fibrosis induced by unilateral ureteral obstruction and metastasis of human cancer xenografts are suppressed by administration of secreted Klotho protein to mice. Klotho is a single-pass transmembrane protein expressed in renal tubular epithelial cells. The extracellular domain of Klotho is secreted by ectodomain shedding. Secreted Klotho protein directly binds to the type-II TGF-β receptor and inhibits TGF-β1 binding to cell surface receptors, thereby inhibiting TGF-β1 signaling. Klotho suppresses TGF-β1-induced epithelial-to-mesenchymal transition (EMT) responses in cultured cells, including decreased epithelial marker expression, increased mesenchymal marker expression, and/or increased cell migration. In addition to TGF-β1 signaling, secreted Klotho has been shown to inhibit Wnt and IGF-1 signaling that can promote EMT. These results have raised the possibility that secreted Klotho may function as an endogenous anti-EMT factor by inhibiting multiple growth factor signaling pathways simultaneously.
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Cites
Epithelial-Mesenchymal Transitions in Development and Disease
Thiery, J. P., Acloque, H., Huang, R. Y. J., & Nieto, M. A. (2009) · Cell · doi:10.1016/j.cell.2009.11.007 · Cited by 9,931
Prevalence of Chronic Kidney Disease in the United States
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Mutation of the mouse klotho gene leads to a syndrome resembling ageing
Kuro-o, M., Matsumura, Y., Aizawa, H., Kawaguchi, H., Suga, T., Utsugi, T., Ohyama, Y., Kurabayashi, M., Kaname, T., Kume, E., et al. (1997) · Nature · doi:10.1038/36285 · Cited by 3,837
Self-citationBiomarkers for epithelial-mesenchymal transitions
Zeisberg, M., & Neilson, E. G. (2009) · Journal of Clinical Investigation · doi:10.1172/jci36183 · Cited by 2,299
Tankyrase inhibition stabilizes axin and antagonizes Wnt signalling
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Suppression of Aging in Mice by the Hormone Klotho
Kurosu, H., Yamamoto, M., Clark, J. D., Pastor, J. V., Nandi, A., Gurnani, P., McGuinness, O. P., Chikuda, H., Yamaguchi, M., Kawaguchi, H., et al. (2005) · Science · doi:10.1126/science.1112766 · Cited by 1,935
Self-citationFGF-23 Is a Potent Regulator of Vitamin D Metabolism and Phosphate Homeostasis
Shimada, T., Hasegawa, H., Yamazaki, Y., Muto, T., Hino, R., Takeuchi, Y., Fujita, T., Nakahara, K., Fukumoto, S., & Yamashita, T. (2004) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.0301264 · Cited by 1,883
SPECIFICITY AND VERSATILITY IN TGF-β SIGNALING THROUGH SMADS
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Klotho converts canonical FGF receptor into a specific receptor for FGF23
Urakawa, I., Yamazaki, Y., Shimada, T., Iijima, K., Hasegawa, H., Okawa, K., Fujita, T., Fukumoto, S., & Yamashita, T. (2006) · Nature · doi:10.1038/nature05315 · Cited by 1,850
Evidence that fibroblasts derive from epithelium during tissue fibrosis
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Cited by
TGF-β: the master regulator of fibrosis
Meng, X.-M., Nikolic-Paterson, D. J., & Lan, H. Y. (2016) · Nature Reviews Nephrology · doi:10.1038/nrneph.2016.48 · Cited by 3,528
The Klotho proteins in health and disease
Kuro-o, M. (2019) · Nature Reviews Nephrology · doi:10.1038/s41581-018-0078-3 · Cited by 707
Self-citationHu, M. C., Shiizaki, K., Kuro-o, M., & Moe, O. W. (2013) · Annual Review of Physiology · doi:10.1146/annurev-physiol-030212-183727 · Cited by 587
Self-citationMolecular Basis of Klotho: From Gene to Function in Aging
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PAI-1–regulated extracellular proteolysis governs senescence and survival in Klotho mice
Eren, M., Boe, A. E., Murphy, S. B., Place, A. T., Nagpal, V., Morales-Nebreda, L., Urich, D., Quaggin, S. E., Budinger, G. R. S., Mutlu, G. M., et al. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1321942111 · Cited by 176
Metadata
- Authors
- Doi, S., Zou, Y., Togao, O., Pastor, J. V., John, G. B., Wang, L., Shiizaki, K., Gotschall, R., Schiavi, S., Yorioka, N., Takahashi, M., Boothman, D. A., & Kuro-o, M.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2011-03
- Volume
- 286
- Issue
- 10
- Pages
- 8655-8665
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2087544898
- Cited by
- 532
- References
- 52
- FWCI
- 12.70
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- CoChat. (2026). Citation check: Klotho Inhibits Transforming Growth Factor-β1 (TGF-β1) Signaling and Suppresses Renal Fibrosis and Cancer Metastasis in Mice. https://app.cochat.ai/papers/10.1074/jbc.m110.174037
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- Doi, S., Zou, Y., Togao, O., Pastor, J. V., John, G. B., Wang, L., Shiizaki, K., Gotschall, R., Schiavi, S., Yorioka, N., Takahashi, M., Boothman, D. A., & Kuro-o, M. (2011). Klotho Inhibits Transforming Growth Factor-β1 (TGF-β1) Signaling and Suppresses Renal Fibrosis and Cancer Metastasis in Mice. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.m110.174037
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
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.
