The DOI matches its Crossref record; 63 of the 63 references it cites were found in a registry or an index.
Klotho: a novel phosphaturic substance acting as an autocrine enzyme in the renal proximal tubule
Open accessAbstract
Klotho has profound effects on phosphate metabolism, but the mechanisms of how Klotho affects phosphate homeostasis is unknown. We detected Klotho in the proximal tubule cell, brush border, and urinary lumen, where phosphate homeostasis resides. Increasing Klotho in the kidney and urine chronically by transgenic overexpression or acutely by intravenous infusion caused hypophosphatemia, phosphaturia from decreased proximal phosphate reabsorption, and decreased activity and protein of the principal renal phosphate transporter NaPi‐2a. The phosphaturic effect was present in FGF23‐null mice, indicating a direct action distinct from Klotho's known role as a coreceptor for FGF23. Direct inhibition of NaPi‐2a by Klotho was confirmed in cultured cells and in cell‐free membrane vesicles characterized by acute inhibition of transport activity followed by decreased cell surface protein. Transport inhibition can be mimicked by recombinant β‐glucuronidase and is associated with proteolytic degradation and reduced surface NaPi‐2a. The inhibitory effect of Klotho on NaPi‐2a was blocked by β‐glucuronidase inhibitor but not by protease inhibitor. Klotho is a novel phosphaturic substance that acts as an enzyme in the proximal tubule urinary lumen by modifying glycans, which cause decreased transporter activity, followed by proteolytic degradation and possibly internalization of NaPi‐2a from the apical membrane.—Hu, M. C., Shi, M., Zhang, J., Pastor, J., Nakatani, T., Lanske, B., Shawkat Razzaque, M., Rosenblatt, K. P., Baum, M. G., Kuro‐o, M., Moe, O. W. Klotho: a novel phosphaturic substance acting as an autocrine enzyme in the renal proximal tubule. FASEB J . 24, 3438–3450 (2010). www.fasebj.org
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Cites
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-citationSuppression 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-citationKlotho 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
Shimada, T., Kakitani, M., Yamazaki, Y., Hasegawa, H., Takeuchi, Y., Fujita, T., Fukumoto, S., Tomizuka, K., & Yamashita, T. (2004) · Journal of Clinical Investigation · doi:10.1172/jci19081 · Cited by 1,596
Regulation of Fibroblast Growth Factor-23 Signaling by Klotho
Kurosu, H., Ogawa, Y., Miyoshi, M., Yamamoto, M., Nandi, A., Rosenblatt, K. P., Baum, M. G., Schiavi, S., Hu, M.-C., Moe, O. W., et al. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.c500457200 · Cited by 1,366
Self-citationThe parathyroid is a target organ for FGF23 in rats
Ben-Dov, I. Z., Galitzer, H., Lavi-Moshayoff, V., Goetz, R., Kuro-o, M., Mohammadi, M., Sirkis, R., Naveh-Many, T., & Silver, J. (2007) · Journal of Clinical Investigation · doi:10.1172/jci32409 · Cited by 951
Self-citationImmunochemistry on ultrathin frozen sections
Tokuyasu, K. T. (1980) · The Histochemical Journal · doi:10.1007/bf01011956 · Cited by 751
Regulation of Oxidative Stress by the Anti-aging Hormone Klotho*♦
Yamamoto, M., Clark, J. D., Pastor, J. V., Gurnani, P., Nandi, A., Kurosu, H., Miyoshi, M., Ogawa, Y., Castrillon, D. H., Rosenblatt, K. P., et al. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m509039200 · Cited by 724
Self-citationMatsumura, Y., Aizawa, H., Shiraki-Iida, T., Nagai, R., Kuro-o, M., & Nabeshima, Y.-I. (1998) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1997.8019 · Cited by 674
Self-citationThe ß-Glucuronidase Klotho Hydrolyzes and Activates the TRPV5 Channel
Chang, Q., Hoefs, S., van der Kemp, A. W., Topala, C. N., Bindels, R. J., & Hoenderop, J. G. (2005) · Science · doi:10.1126/science.1114245 · Cited by 622
Cited by
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-citationRegulation and Function of the FGF23/Klotho Endocrine Pathways
Martin, A., David, V., & Quarles, L. D. (2012) · Physiological Reviews · doi:10.1152/physrev.00002.2011 · Cited by 594
Hu, 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
Xu, Y., & Sun, Z. (2015) · Endocrine Reviews · doi:10.1210/er.2013-1079 · Cited by 549
Doi, S., Zou, Y., Togao, O., Pastor, J. V., John, G. B., Wang, L., Shiizaki, K., Gotschall, R., Schiavi, S., Yorioka, N., et al. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.174037 · Cited by 532
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Metadata
- Authors
- Hu, M. C., Shi, M., Zhang, J., Pastor, J., Nakatani, T., Lanske, B., Razzaque, M. S., Rosenblatt, K. P., Baum, M. G., Kuro‐O, M., & Moe, O. W.
- Venue
- The FASEB Journal
- Publisher
- Wiley
- Published
- 2010-05-13
- Volume
- 24
- Issue
- 9
- Pages
- 3438-3450
- ISSN
- 0892-6638 (ISSN-L)
- 1530-6860
- OpenAlex
- W2106711282
- Cited by
- 578
- References
- 63
- FWCI
- 32.23
- Type
- journal article
- Language
- en
- Open access
- green
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