The DOI matches its Crossref record; 27 of the 27 references it cites were found in a registry or an index.
Targeted proximal tubule injury triggers interstitial fibrosis and glomerulosclerosis
Open accessAbstract
Chronic kidney disease (CKD) remains one of the leading causes of death in the developed world and acute kidney injury (AKI) is now recognized as a major risk factor in its development. Understanding the factors leading to CKD after acute injury are limited by current animal models of AKI which concurrently target various kidney cell types such as epithelial, endothelial and inflammatory cells. Here we developed a mouse model of kidney injury using the Six2-Cre-LoxP technology to selectively activate expression of the simian diphtheria toxin receptor in renal epithelia derived from the metanephric mesenchyme. By adjusting the timing and dose of diphtheria toxin a highly selective model of tubular injury was created to define the acute and chronic consequences of isolated epithelial injury. The diphtheria toxin-induced sublethal tubular epithelial injury was confined to the S1 and S2 segments of the proximal tubule rather than being widespread in the metanephric mesenchyme derived epithelial lineage. Acute injury was promptly followed by inflammatory cell infiltration and robust tubular cell proliferation leading to complete recovery after a single toxin insult. In striking contrast, three insults to renal epithelial cells at one week intervals resulted in maladaptive repair with interstitial capillary loss, fibrosis and glomerulosclerosis which was highly correlated with the degree of interstitial fibrosis. Thus, selective epithelial injury can drive the formation of interstitial fibrosis, capillary rarefaction and potentially glomerulosclerosis, substantiating a direct role for damaged tubule epithelium in the pathogenesis of CKD.
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Cites
Acute Kidney Injury, Mortality, Length of Stay, and Costs in Hospitalized Patients
Chertow, G. M., Burdick, E., Honour, M., Bonventre, J. V., & Bates, D. W. (2005) · Journal of the American Society of Nephrology · doi:10.1681/asn.2004090740 · Cited by 3,408
Self-citationFate Tracing Reveals the Pericyte and Not Epithelial Origin of Myofibroblasts in Kidney Fibrosis
Humphreys, B. D., Lin, S.-L., Kobayashi, A., Hudson, T. E., Nowlin, B. T., Bonventre, J. V., Valerius, M. T., McMahon, A. P., & Duffield, J. S. (2010) · The American Journal of Pathology · doi:10.2353/ajpath.2010.090517 · Cited by 1,442
Self-citationThadhani, R., Pascual, M., & Bonventre, J. V. (1996) · New England Journal of Medicine · doi:10.1056/nejm199605303342207 · Cited by 1,417
Self-citationEpithelial cell cycle arrest in G2/M mediates kidney fibrosis after injury
Yang, L., Besschetnova, T. Y., Brooks, C. R., Shah, J. V., & Bonventre, J. V. (2010) · Nature Medicine · doi:10.1038/nm.2144 · Cited by 1,333
Self-citationKobayashi, A., Valerius, M. T., Mugford, J. W., Carroll, T. J., Self, M., Oliver, G., & McMahon, A. P. (2008) · Cell Stem Cell · doi:10.1016/j.stem.2008.05.020 · Cited by 973
A Cre-inducible diphtheria toxin receptor mediates cell lineage ablation after toxin administration
Buch, T., Heppner, F. L., Tertilt, C., Heinen, T. J. A. J., Kremer, M., Wunderlich, F. T., Jung, S., & Waisman, A. (2005) · Nature Methods · doi:10.1038/nmeth762 · Cited by 921
Intrinsic Epithelial Cells Repair the Kidney after Injury
Humphreys, B. D., Valerius, M. T., Kobayashi, A., Mugford, J. W., Soeung, S., Duffield, J. S., McMahon, A. P., & Bonventre, J. V. (2008) · Cell Stem Cell · doi:10.1016/j.stem.2008.01.014 · Cited by 868
Self-citationLin, S.-L., Kisseleva, T., Brenner, D. A., & Duffield, J. S. (2008) · The American Journal of Pathology · doi:10.2353/ajpath.2008.080433 · Cited by 845
TLR4 activation mediates kidney ischemia/reperfusion injury
Wu, H., Chen, G., Wyburn, K. R., Yin, J., Bertolino, P., Eris, J. M., Alexander, S. I., Sharland, A. F., & Chadban, S. J. (2007) · Journal of Clinical Investigation · doi:10.1172/jci31008 · Cited by 836
Ischemic acute renal failure: An inflammatory disease?
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Cited by
Renal tubule injury: a driving force toward chronic kidney disease
Liu, B.-C., Tang, T.-T., Lv, L.-L., & Lan, H.-Y. (2018) · Kidney International · doi:10.1016/j.kint.2017.09.033 · Cited by 913
Organ and tissue fibrosis: Molecular signals, cellular mechanisms and translational implications
Weiskirchen, R., Weiskirchen, S., & Tacke, F. (2019) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2018.06.003 · Cited by 538
See, E. J., Jayasinghe, K., Glassford, N., Bailey, M., Johnson, D. W., Polkinghorne, K. R., Toussaint, N. D., & Bellomo, R. (2019) · Kidney International · doi:10.1016/j.kint.2018.08.036 · Cited by 532
AKI on CKD: heightened injury, suppressed repair, and the underlying mechanisms
He, L., Wei, Q., Liu, J., Yi, M., Liu, Y., Liu, H., Sun, L., Peng, Y., Liu, F., Venkatachalam, M. A., et al. (2017) · Kidney International · doi:10.1016/j.kint.2017.06.030 · Cited by 448
Immune cells and inflammation in AKI to CKD progression
Sato, Y., & Yanagita, M. (2018) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00195.2018 · Cited by 273
Metadata
- Authors
- Grgic, I., Campanholle, G., Bijol, V., Wang, C., Sabbisetti, V. S., Ichimura, T., Humphreys, B. D., & Bonventre, J. V.
- Venue
- Kidney International
- Publisher
- Elsevier BV
- Published
- 2012-07
- Volume
- 82
- Issue
- 2
- Pages
- 172-183
- ISSN
- 0085-2538 (ISSN-L)
- OpenAlex
- W2068050227
- Cited by
- 477
- References
- 27
- FWCI
- 22.58
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Grgic, I., Campanholle, G., Bijol, V., Wang, C., Sabbisetti, V. S., Ichimura, T., Humphreys, B. D., & Bonventre, J. V. (2012). Targeted proximal tubule injury triggers interstitial fibrosis and glomerulosclerosis. Kidney International. https://doi.org/10.1038/ki.2012.20
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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