YKL-40, a Marker of Simian Immunodeficiency Virus Encephalitis, Modulates the Biological Activity of Basic Fibroblast Growth Factor

Bonneh‐Barkay, Dafna; Bissel, Stephanie J.; Wang, Gouji; Fish, Kenneth N.; Nicholl, Georgina C.B.; Darko, Samuel; Medina‐Flores, Rafael; Murphey‐Corb, Michael; Rajakumar, Premeela A.; Nyaundi, Julia; Mellors, John W.; Bowser, Robert; Wiley, Clayton A.

doi:10.2353/ajpath.2008.080045

Cited by 123 publications

(109 citation statements)

References 69 publications

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“…33 In contrast to MCP-1, YKL-40 appears to be more expressed in microglia than in neurons or astrocytes. 34 Increased YKL-40 expression is characteristic of many chronic inflammatory conditions, such as rheumatoid arthritis and irritable bowel syndrome, that are associated with destruction of the extracellular matrix and tissue remodelling. 35 It is therefore conceivable that YKL-40 causes remodelling of the extracellular matrix in the brain that could lead to neuronal dysfunction.…”

Section: Discussionmentioning

confidence: 99%

Monocyte and microglial activation in patients with mood-stabilized bipolar disorder

Jakobsson

Bjerke

Sahebi

et al. 2015

jpn

100

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Section: Discussionmentioning

confidence: 99%

Monocyte and microglial activation in patients with mood-stabilized bipolar disorder

Jakobsson

Bjerke

Sahebi

et al. 2015

jpn

100

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“…YKL-40 levels are also elevated in patients with a wide array of pathologies characterized by tissue destruction, ongoing inflammation, and development of fibrosis, such as rheumatoid arthritis, atherosclerosis, osteoarthritis, giant cell arthritis, and sarcoidosis (17), implicating its role in inflammatory processes and tissue remodeling. Increased levels of YKL-40 have also been reported in CNS pathologies, including Alzheimer disease, HIV-associated dementia, and multiple sclerosis (22)(23)(24). Although YKL-40 is produced by activated microglia (23), it has recently been shown that it is also secreted by reactive astrocytes (25).…”

mentioning

confidence: 99%

“…Increased levels of YKL-40 have also been reported in CNS pathologies, including Alzheimer disease, HIV-associated dementia, and multiple sclerosis (22)(23)(24). Although YKL-40 is produced by activated microglia (23), it has recently been shown that it is also secreted by reactive astrocytes (25).…”

mentioning

confidence: 99%

A Complex of Nuclear Factor I-X3 and STAT3 Regulates Astrocyte and Glioma Migration through the Secreted Glycoprotein YKL-40

Singh

Bhardwaj

Wilczynska

et al. 2011

Journal of Biological Chemistry

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Nuclear factor I-X3 (NFI-X3) is a newly identified splice variant of NFI-X that regulates expression of several astrocyte-specific markers, such as glial fibrillary acidic protein. Here, we identified a set of genes regulated by NFI-X3 that includes a gene encoding a secreted glycoprotein YKL-40. Although YKL-40 expression is up-regulated in glioblastoma multiforme, its regulation and functions in nontransformed cells of the central nervous system are widely unexplored. We find that expression of YKL-40 is activated during brain development and also differentiation of neural progenitors into astrocytes in vitro. Furthermore, YKL-40 is a migration factor for primary astrocytes, and its expression is controlled by both NFI-X3 and STAT3, which are known regulators of gliogenesis. Knockdown of NFI-X3 and STAT3 significantly reduced YKL-40 expression in astrocytes, whereas overexpression of NFI-X3 dramatically enhanced YKL-40 expression in glioma cells. Activation of STAT3 by oncostatin M induced YKL-40 expression in astrocytes, whereas expression of a dominant-negative STAT3 had a suppressive effect. Mechanistically, NFI-X3 and STAT3 form a complex that binds to weak regulatory elements in the YKL-40 promoter and activates transcription. We propose that NFI-X3 and STAT3 control the migration of differentiating astrocytes as well as migration and invasion of glioma cells via regulating YKL-40 expression.Astrocytes, the most abundant CNS cells, are critical for many functions of normal and pathological brains (1, 2). Generation and differentiation of astrocytes from neural progenitors is controlled by activation of the JAK-STAT3, BMP-SMAD, and Notch-HES pathways in vivo (3, 4) and promoted by cytokines of the IL-6 family that activate STAT3 in vitro (5, 6). In addition to these pathways, evolutionarily conserved NFI 3 transcription factors, consisting of NFI-A, -B, -C, and -X, regulate astrocyte differentiation (7,8). NFIs are expressed in overlapping patterns during embryogenesis, with high expression levels of NFI-A, -B, and -X found in the developing neocortex (9, 10). Consequently, Nfia, Nfib, and Nfix knock-out mice show severe brain anatomical defects, including agenesis of corpus callosum (9, 10), whereas NPs from Nfix knock-out mice show defects in proliferation and migration (9, 10). NFI-A and -B control gliogenesis in chick embryonic spinal cord (7), whereas NFI-X and -C regulate the expression of late astrocyte markers during the differentiation of human NPs in vitro (7,8). Expression of NFI-A is induced by Notch signaling in NP and leads to the demethylation of astrocyte-specific genes (11), as well as down-regulation of Notch signaling via repression of Notch effector Hes1 (12). Each of the NFI transcripts undergoes alternative splicing, generating as many as nine different NFI splice variants (13), likely possessing distinctive functions. We have recently characterized a novel human NFI-X3 splice variant, which is a potent activator of gene expression in astrocytes (14). NFI-X3 contains a unique transcri...

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“…CHI3L1 modulates activity of basic fibroblast growth factor (bFGF) [49], binds to collagen types I, II, and III, and modulates the rate of collagen fibril formation [48]. No one of these interactions is shown for CHI3L2, and no protein-protein interaction partners were found up to now (particularly, there are no reports about participation of CHI3L2 in any proteinprotein interaction in BioGRID, HPID, MIPS, MINT, IntAct, DIP, and BRITE databases).…”

Section: Discussionmentioning

confidence: 99%

Homology modeling of 3D structure of human chitinase-like protein CHI3L2

et al. 2010

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Abstract:The human genome encodes six proteins of family 18 glycosyl hydrolases, two active chitinases and four chitinase-like lectins (chilectins) lacking catalytic activity. The present article is dedicated to homology modeling of 3D structure of human chitinase 3-like 2 protein (CHI3L2), which is overexpressed in glial brain tumors, and its structural comparison with homologous chi-lectin CHI3L1. Two crystal structures of CHI3L1 in free state (Protein Data Bank codes 1HJX and 1NWR) were used as structural templates for the homology modeling by Modeller 9.7 program, and the best quality model structure was selected from the obtained model ensemble.Analysis of potential oligosaccharide-binding groove structures of CHI3L1 and CHI3L2 revealed significant differences between these two homologous proteins. . The differences between these residues could influence the structure of the ligand-binding groove and substantially change the ability of CHI3L2 to bind oligosaccharide ligands. © Versita Sp. z o.o.

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YKL-40, a Marker of Simian Immunodeficiency Virus Encephalitis, Modulates the Biological Activity of Basic Fibroblast Growth Factor

Abstract: Human immunodeficiency virus encephalitis causes

Cited by 123 publications

References 69 publications

Monocyte and microglial activation in patients with mood-stabilized bipolar disorder

Monocyte and microglial activation in patients with mood-stabilized bipolar disorder

A Complex of Nuclear Factor I-X3 and STAT3 Regulates Astrocyte and Glioma Migration through the Secreted Glycoprotein YKL-40

Homology modeling of 3D structure of human chitinase-like protein CHI3L2

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