The DOI matches its Crossref record; 12 of the 12 references it cites were found in a registry or an index.
Lipocalin-2 Is an Autocrine Mediator of Reactive Astrocytosis
Open accessAbstract
Astrocytes, the most abundant glial cell type in the brain, provide metabolic and trophic support to neurons and modulate synaptic activity. In response to a brain injury, astrocytes proliferate and become hypertrophic with an increased expression of intermediate filament proteins. This process is collectively referred to as reactive astrocytosis. Lipocalin 2 (lcn2) is a member of the lipocalin family that binds to small hydrophobic molecules. We propose that lcn2 is an autocrine mediator of reactive astrocytosis based on the multiple roles of lcn2 in the regulation of cell death, morphology, and migration of astrocytes. lcn2 expression and secretion increased after inflammatory stimulation in cultured astrocytes. Forced expression of lcn2 or treatment with LCN2 protein increased the sensitivity of astrocytes to cytotoxic stimuli. Iron and BIM (Bcl-2-interacting mediator of cell death) proteins were involved in the cytotoxic sensitization process. LCN2 protein induced upregulation of glial fibrillary acidic protein (GFAP), cell migration, and morphological changes similar to characteristic phenotypic changes termed reactive astrocytosis. The lcn2-induced phenotypic changes of astrocytes occurred through a Rho–ROCK (Rho kinase)–GFAP pathway, which was positively regulated by nitric oxide and cGMP. In zebrafishes, forced expression of rat lcn2 gene increased the number and thickness of cellular processes in GFAP-expressing radial glia cells, suggesting that lcn2 expression in glia cells plays an important role in vivo. Our results suggest that lcn2 acts in an autocrine manner to induce cell death sensitization and morphological changes in astrocytes under inflammatory conditions and that these phenotypic changes may be the basis of reactive astrocytosis in vivo.
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Cites
Astrocytes are active players in cerebral innate immunity
Farina, C., Aloisi, F., & Meinl, E. (2007) · Trends in Immunology · doi:10.1016/j.it.2007.01.005 · Cited by 1,304
Mori, K., Lee, H. T., Rapoport, D., Drexler, I. R., Foster, K., Yang, J., Schmidt-Ott, K. M., Chen, X., Li, J. Y., Weiss, S., et al. (2005) · Journal of Clinical Investigation · doi:10.1172/jci23056 · Cited by 954
Self-citationThe lipocalin protein family: structural and sequence overview
Flower, D. R., North, A. C. T., & Sansom, C. E. (2000) · Biochimica et Biophysica Acta (BBA) - Protein Structure and Molecular Enzymology · doi:10.1016/s0167-4838(00)00148-5 · Cited by 868
An Iron Delivery Pathway Mediated by a Lipocalin
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Self-citationWilhelmsson, U., Bushong, E. A., Price, D. L., Smarr, B. L., Phung, V., Terada, M., Ellisman, M. H., & Pekny, M. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0602841103 · Cited by 643 · cited 1×
“This type of morphological change in astrocytes is similar to what occurs in reactive astrocytosis in vivo (Boukhelifa et al., 2003; Lin and Cai, 2004; Wilhelmsson et al., 2006).”
ResultHerbomel, P., Thisse, B., & Thisse, C. (2001) · Developmental Biology · doi:10.1006/dbio.2001.0393 · Cited by 574
Organization of hindbrain segments in the zebrafish embryo
Trevarrow, B., Marks, D. L., & Kimmel, C. B. (1990) · Neuron · doi:10.1016/0896-6273(90)90194-k · Cited by 506
Wilhelmsson, U., Li, L., Pekna, M., Berthold, C.-H., Blom, S., Eliasson, C., Renner, O., Bushong, E., Ellisman, M., Morgan, T. E., et al. (2004) · The Journal of Neuroscience · doi:10.1523/jneurosci.0820-04.2004 · Cited by 455
Human neutrophil gelatinase-associated lipocalin and homologous proteins in rat and mouse
Kjeldsen, L., Cowland, J. B., & Borregaard, N. (2000) · Biochimica et Biophysica Acta (BBA) - Protein Structure and Molecular Enzymology · doi:10.1016/s0167-4838(00)00152-7 · Cited by 368
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Cited by
Molecular dissection of reactive astrogliosis and glial scar formation
Sofroniew, M. V. (2009) · Trends in Neurosciences · doi:10.1016/j.tins.2009.08.002 · Cited by 2,594
Genomic analysis of reactive astrogliosis
Zamanian, J. L., Xu, L., Foo, L. C., Nouri, N., Zhou, L., Giffard, R. G., & Barres, B. A. (2012) · The Journal of Neuroscience · doi:10.1523/jneurosci.6221-11.2012 · Cited by 2,404
Microglia-Astrocyte Crosstalk: An Intimate Molecular Conversation
Jha, M. K., Jo, M., Kim, J.-H., & Suk, K. (2019) · The Neuroscientist · doi:10.1177/1073858418783959 · Cited by 579
Self-citationLipocalin 2: an emerging player in iron homeostasis and inflammation
Xiao, X., Yeoh, B. S., & Vijay-Kumar, M. (2017) · Annual Review of Nutrition · doi:10.1146/annurev-nutr-071816-064559 · Cited by 426
Astrocyte Heterogeneity: Impact to Brain Aging and Disease
Matias, I., Morgado, J., & Gomes, F. C. A. (2019) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2019.00059 · Cited by 387
Metadata
- Authors
- Lee, S., Park, J.-Y., Lee, W.-H., Kim, H., Park, H.-C., Mori, K., & Suk, K.
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2009-01-07
- Volume
- 29
- Issue
- 1
- Pages
- 234-249
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- OpenAlex
- W2162325038
- Cited by
- 280
- References
- 12
- FWCI
- 9.02
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Lee, S., Park, J.-Y., Lee, W.-H., Kim, H., Park, H.-C., Mori, K., & Suk, K. (2009). Lipocalin-2 Is an Autocrine Mediator of Reactive Astrocytosis. The Journal of Neuroscience. https://doi.org/10.1523/jneurosci.5273-08.2009
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