Functional analysis of the short splicing variant encoded by CHI3L1/YKL-40 in glioblastoma

Shi, Mengqi; Ge, Qian; Wang, Xinrong; Diao, Wenbin; Yang, Ben; Sun, Sipeng; Wang, Guohui; Liu, Tian; Chan, Andrew M.; Gao, Zhiqin; Wang, Yi; Wang, Yubing

doi:10.3389/fonc.2022.910728

Cited by 2 publications

(2 citation statements)

References 37 publications

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“…A detailed expression analysis would be required to address the relative abundance of these receptors in mouse astrocytes. For potential intracellular targets for YKL-40, we have recently demonstrated the nuclear localization of YKL-40 in human glioblastoma cell lines [ 55 ]. Whether YKL-40 has direct transcriptional activity on gene expression could be an area of future investigation.…”

Section: Discussionmentioning

confidence: 99%

Astrocyte-specific knockout of YKL-40/Chi3l1 reduces Aβ burden and restores memory functions in 5xFAD mice

Zeng,

Cheung,

Shi

et al. 2023

J Neuroinflammation

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Glial cell-mediated neuroinflammation and neuronal attrition are highly correlated with cognitive impairment in Alzheimer’s disease. YKL-40 is a secreted astrocytic glycoprotein that serves as a diagnostic biomarker of Alzheimer’s disease. High levels of YKL-40 are associated with either advanced Alzheimer’s disease or the normal aging process. However, the functional role of YKL-40 in Alzheimer’s disease development has not been firmly established. In a 5xFAD mouse model of Alzheimer’s disease, we observed increased YKL-40 expression in the cerebrospinal fluid of 7-month-old mice and was correlated with activated astrocytes. In primary astrocytes, Aβ1-42 upregulated YKL-40 in a dose-dependent manner and was correlated with PI3-K signaling pathway activation. Furthermore, primary neurons treated with YKL-40 and/or Aβ1-42 resulted in significant synaptic degeneration, reduced dendritic complexity, and impaired electrical parameters. More importantly, astrocyte-specific knockout of YKL-40 over a period of 7 days in symptomatic 5xFAD mice could effectively reduce amyloid plaque deposition in multiple brain regions. This was also associated with attenuated glial activation, reduced neuronal attrition, and restored memory function. These biological phenotypes could be explained by enhanced uptake of Aβ1-42 peptides, increased rate of Aβ1-42 degradation and acidification of lysosomal compartment in YKL-40 knockout astrocytes. Our results provide new insights into the role of YKL-40 in Alzheimer’s disease pathogenesis and demonstrate the potential of targeting this soluble biomarker to alleviate cognitive defects in symptomatic Alzheimer’s disease patients.

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Section: Discussionmentioning

confidence: 99%

Astrocyte-specific knockout of YKL-40/Chi3l1 reduces Aβ burden and restores memory functions in 5xFAD mice

Zeng,

Cheung,

Shi

et al. 2023

J Neuroinflammation

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“…This molecule appears to be a favorable CC biomarker in both SSC and adenocarcinoma subtypes, and it appears to be more specific than SCC-A and CA125. Previous findings demonstrated that serum YKL-40 level is increased in several solid tumors with a variety of histological types (37,38). This protein is a biomarker associated with inflammation and, despite this, it could be a correlation between the C-reactive protein (CRP) and YKL-40 (39).…”

Section: Proteinsmentioning

confidence: 99%

Circulating cervical cancer biomarkers potentially useful in medical attention (Review)

Garrido

Gutiérrez²,

Flores

2023

Mol Clin Oncol

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Cervical cancer (CC) is a public health problem worldwide, including Mexico. This type of cancer is the fourth most frequent in women worldwide; in Mexico it is the second most common type in women after breast cancer. The diagnosis of CC is based mainly on Pap smears and colposcopy and the identification of molecular tools that serve as a support for these methods is urgent. Regarding this, differential expressions of specific circulating biomolecules has been detected and, based on this, they have been postulated as potential biomarkers for CC diagnosis, prognosis, and/or to identify the response to treatments. Importantly, the combined analysis of these molecules considerably improves their efficacy as biomarkers and their potential use in the medical attention is promising. Contents1. Introduction 2. Proteins 3. ncRNAs 4. The estrogen effect on the expression of biomarkers 5. cDNA 6. Putative molecular mechanisms altered by the CC biomarkers 7. Circulating biomarkers expression in other HPV-related cancers 8. How feasible is it to use a test of this type in the heath sector of undeveloped countries? 9. The best biomarkers panel, according to our point of view 10. Conclusions and future directions

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Functional analysis of the short splicing variant encoded by CHI3L1/YKL-40 in glioblastoma

Cited by 2 publications

References 37 publications

Astrocyte-specific knockout of YKL-40/Chi3l1 reduces Aβ burden and restores memory functions in 5xFAD mice

Astrocyte-specific knockout of YKL-40/Chi3l1 reduces Aβ burden and restores memory functions in 5xFAD mice

Circulating cervical cancer biomarkers potentially useful in medical attention (Review)

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