The DOI matches its Crossref record; 40 of the 40 references it cites were found in a registry or an index.
Shedding of Kidney Injury Molecule-1, a Putative Adhesion Protein Involved in Renal Regeneration
Open accessAbstract
KIM-1 (kidney injury molecule-1) is a type I transmembrane glycoprotein expressed on dedifferentiated renal proximal tubule epithelial cells undergoing regeneration after toxic or ischemic injury. The extracellular domain of KIM-1 is composed of an immunoglobulin-like domain topping a long mucin-like domain, a structure that points to a possible role in cell adhesion by homology to several known adhesion proteins. Two splice variants (a and b), of the human KIM-1 having identical extracellular domains, differ in their cytoplasmic domains and tissue distributions. In this study, we report that the KIM-1b transcript is expressed predominantly in adult human kidney. We describe the generation of 10 monoclonal antibodies against the extracellular domain of human KIM-1, the mapping of their binding sites, and their use in identifying various forms of the protein. We show that human KIM-1b is expressed in adult kidney cell lines, and we demonstrate that a soluble form of KIM-1 is shed constitutively into the culture medium of the cell lines expressing endogenous or recombinant KIM-1b by membrane-proximal cleavage. A monoclonal antibody that binds at or close to the proteolytic site can partially block the shedding of KIM-1. Release of soluble KIM-1 is enhanced by activating the cells with phorbol 12-myristate 13-acetate and can be inhibited with two metalloproteinase inhibitors, BB-94 (Batimastat) and GM6001 (Ilomastat), suggesting that the cleavage is mediated by a metalloproteinase. We propose that the shedding of KIM-1 in the kidney undergoing regeneration constitutes an active mechanism allowing dedifferentiated regenerating cells to scatter on denuded patches of the basement membrane and reconstitute a continuous epithelial layer.
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Cites
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Kidney Injury Molecule-1 (KIM-1): A novel biomarker for human renal proximal tubule injury
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Self-citationAn Essential Role for Ectodomain Shedding in Mammalian Development
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Cited by
Mishra, J., Ma, Q., Prada, A., Mitsnefes, M., Zahedi, K., Yang, J., Barasch, J., & Devarajan, P. (2003) · Journal of the American Society of Nephrology · doi:10.1097/01.asn.0000088027.54400.c6 · Cited by 1,749
Update on Mechanisms of Ischemic Acute Kidney Injury
Devarajan, P. (2006) · Journal of the American Society of Nephrology · doi:10.1681/asn.2006010017 · Cited by 1,026
The TIM gene family: emerging roles in immunity and disease
Kuchroo, V. K., Umetsu, D. T., DeKruyff, R. H., & Freeman, G. J. (2003) · Nature Reviews Immunology · doi:10.1038/nri1111 · Cited by 388
Devarajan, P., Mishra, J., Supavekin, S., Patterson, L. T., & Steven Potter, S. (2003) · Molecular Genetics and Metabolism · doi:10.1016/j.ymgme.2003.09.012 · Cited by 229
TIM-2 is expressed on B cells and in liver and kidney and is a receptor for H-ferritin endocytosis
Chen, T. T., Li, L., Chung, D.-H., Allen, C. D. C., Torti, S. V., Torti, F. M., Cyster, J. G., Chen, C.-Y., Brodsky, F. M., Niemi, E. C., et al. (2005) · The Journal of Experimental Medicine · doi:10.1084/jem.20042433 · Cited by 219
Metadata
- Authors
- Bailly, V., Zhang, Z., Meier, W., Cate, R., Sanicola, M., & Bonventre, J. V.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2002-10
- Volume
- 277
- Issue
- 42
- Pages
- 39739-39748
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2129003781
- Cited by
- 355
- References
- 40
- FWCI
- 5.74
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Bailly, V., Zhang, Z., Meier, W., Cate, R., Sanicola, M., & Bonventre, J. V. (2002). Shedding of Kidney Injury Molecule-1, a Putative Adhesion Protein Involved in Renal Regeneration. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.m200562200
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