Significance of chitinase-3-like protein 1 in the pathogenesis of inflammatory diseases and cancer

Yu, Ji Eun; Yeo, In Jun; Han, Sang-Bae; Yun, Jaesuk; Kim, Bongcheol; Yong, Yoon Ji; Lim, Young-soo; Kim, Tae Hun; Son, Dong Ju; Hong, Jin Tae

doi:10.1038/s12276-023-01131-9

Cited by 11 publications

(4 citation statements)

References 180 publications

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“…Interestingly, STAT3 is also a downstream signaling protein to CHI3L1 [ 53 ] . Although the exact mechanism of STAT3 activation by CHI3L1 is not fully understood, one possibility is that CHI3L1 activates STAT3 through receptor interaction [ 36 ] . In fact, Lee et al reported that CHI3L1 knockdown decreased STAT3 activity, which in turn decreased cancer cell growth in lung cancer [ 54 ] .…”

Section: Discussionmentioning

confidence: 99%

“…Most importantly, CHI3L activates several pro-survival signaling pathways, and regulates cell growth, differentiation, and apoptosis in NSCLC. For instance, CHI3L1 interacts with IL-13Rα2 and/or the receptor for advanced glycation end products (RAGE), which are transmembrane receptors, activating ERK, Akt, and signal transducer and activator of transcription 3 (STAT3) signaling pathways, and inducing β-catenin nuclear translocation [33][34][35][36] . Thus, inhibitors of CHI3L1 may be promising drugs to be repurposed, in order to be used in NSCLC treatment in combination with chemotherapy.…”

Section: Introductionmentioning

confidence: 99%

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Chemosensitizing effect of pentoxifylline in sensitive and multidrug-resistant non-small cell lung cancer cells

Matos,

Peixoto da Silva,

Vasconcelos

et al. 2024

Cancer Drug Resist

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Aim: Multidrug resistance (MDR) is frequent in non-small cell lung cancer (NSCLC) patients, which can be due to its fibrotic stroma. This work explores the combination of pentoxifylline, an anti-fibrotic and chitinase 3-like-1 (CHI3L1) inhibitor drug, with conventional chemotherapy to improve NSCLC treatment. Methods: The effect of pentoxifylline in the expression levels of P-glycoprotein (P-gp), CHI3L1 and its main downstream proteins, as well as on cell death, cell cycle profile, and P-gp activity was studied in two pairs of sensitive and MDR counterpart NSCLC cell lines (NCI-H460/NCI-H460/R and A549/A549-CDR2). Association studies between CHI3L1 gene expression and NSCLC patients’ survival were performed using The Cancer Genome Atlas (TCGA) analysis. The sensitizing effect of pentoxifylline to different drug regimens was evaluated in both sensitive and MDR NSCLC cell lines. The cytotoxicity of the drug combinations was assessed in MCF10A non-tumorigenic cells. Results: Pentoxifylline slightly decreased the expression levels of CHI3L1, β-catenin and signal transducer and activator of transcription 3 (STAT3), and caused a significant increase in the G1 phase of the cell cycle in both pairs of NSCLC cell lines. A significant increase in the % of cell death was observed in the sensitive NCI-H460 cell line. TCGA analysis revealed that high levels of CHI3L1 are associated with low overall survival (OS) in NSCLC patients treated with vinorelbine. Moreover, pentoxifylline sensitized both pairs of sensitive and MDR NSCLC cell lines to the different drug regimens, without causing significant toxicity to non-tumorigenic cells. Conclusion: This study suggests the possibility of combining pentoxifylline with chemotherapy to increase NSCLC therapeutic response, even in cases of MDR.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Chemosensitizing effect of pentoxifylline in sensitive and multidrug-resistant non-small cell lung cancer cells

Matos,

Peixoto da Silva,

Vasconcelos

et al. 2024

Cancer Drug Resist

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“…CHI3L1 expression is elevated in various inflammatory and chronic diseases, including obesity, diabetes, kidney disease, rheumatoid arthritis, inflammatory bowel disease, cancer, coronary artery disease, and acute ischemic stroke [ 16 – 21 ]. CHI3L1 plays a crucial role in vascular inflammation and atherosclerosis development by promoting EC inflammation and vascular smooth muscle cells migration and value-addition [ 22 ].…”

Section: Discussionmentioning

confidence: 99%

Discovery of crucial cytokines associated with deep vein thrombus formation by protein array analysis

Wang,

Chi,

Zeng

et al. 2024

BMC Cardiovasc Disord

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Background Expanding the number of biomarkers is imperative for studying the etiology and improving venous thromboembolism prediction. In this study, we aimed to identify promising biomarkers or targeted therapies to improve the detection accuracy of early-stage deep vein thrombosis (DVT) or reduce complications. Methods Quantibody Human Cytokine Antibody Array 440 (QAH-CAA-440) was used to screen novel serum-based biomarkers for DVT/non-lower extremity DVT (NDVT). Differentially expressed proteins in DVT were analyzed using bioinformatics methods and validated using a customized array. Diagnostic accuracy was calculated using receiver operating characteristics, and machine learning was applied to establish a biomarker model for evaluating the identified targets. Twelve targets were selected for validation. Results Cytokine profiling was conducted using a QAH-CAA-440 (RayBiotech, USA) quantimeter array. Cross-tabulation analysis with Venn diagrams identified common differential factors, leading to the selection of 12 cytokines for validation based on their clinical significance. These 12 biomarkers were consistent with the results of previous array analysis: FGF-6 (AUC = 0.956), Galectin-3 (AUC = 0.942), EDA-A2 (AUC = 0.933), CHI3L1 (AUC = 0.911), IL-1 F9 (AUC = 0.898), Dkk-4 (AUC = 0.88), IG-H3 (AUC = 0.876), IGFBP (AUC = 0.858), Gas-1 (AUC = 0.858), Layilin (AUC = 0.849), ULBP-2 (AUC = 0.813)and FGF-9 (AUC = 0.773). These cytokines are expected to serve as biomarkers, targets, or therapeutic targets to differentiate DVT from NDVT. Conclusions EDA-A2, FGF-6, Dkk-4, IL-1 F9, Galentin-3, Layilin, Big-h3, CHI3L1, ULBP-2, Gas-1, IGFBP-5, and FGF-9 are promising targets for DVT diagnosis and treatment.

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“…In another study, the significance of chitinase-3-like protein 1 (CHI3L1) as a marker of disease diagnosis, prognosis, activity and severity was appraised. It was further elucidated that the enzyme was upregulated by various inflammatory and immunological diseases, including several cancers, Alzheimer’s disease, and atherosclerosis (Yu et al 2024 ). Chitinase’s deployment in biological warfare could have global implications, affecting regions through environmental contamination and public health risks.…”

Section: Biotechnological Exploits Of Chitinasesmentioning

confidence: 99%

Chitinases: expanding the boundaries of knowledge beyond routinized chitin degradation.

Unuofin,

Odeniyi,

Majengbasan

et al. 2024

Environ Sci Pollut Res

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Chitinases, enzymes that degrade chitin, have long been studied for their role in various biological processes. They play crucial roles in the moulting process of invertebrates, the digestion of chitinous food, and defense against chitin-bearing pathogens. Additionally, chitinases are involved in physiological functions in crustaceans, such as chitinous food digestion, moulting, and stress response. Moreover, chitinases are universally distributed in organisms from viruses to mammals and have diverse functions including tissue degradation and remodeling, nutrition uptake, pathogen invasion, and immune response regulation. The discovery of these diverse functions expands our understanding of the biological significance and potential applications of chitinases. However, recent research has shown that chitinases possess several other functions beyond just chitin degradation. Their potential as biopesticides, therapeutic agents, and tools for bioremediation underscores their significance in addressing global challenges. More importantly, we noted that they may be applied as bioweapons if ethical regulations regarding production, engineering and application are overlooked.

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Significance of chitinase-3-like protein 1 in the pathogenesis of inflammatory diseases and cancer

Cited by 11 publications

References 180 publications

Chemosensitizing effect of pentoxifylline in sensitive and multidrug-resistant non-small cell lung cancer cells

Chemosensitizing effect of pentoxifylline in sensitive and multidrug-resistant non-small cell lung cancer cells

Discovery of crucial cytokines associated with deep vein thrombus formation by protein array analysis

Chitinases: expanding the boundaries of knowledge beyond routinized chitin degradation.

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