Chitinase-like proteins as regulators of innate immunity and tissue repair: helpful lessons for asthma?

Sutherland, Tara E.

doi:10.1042/bst20170108

Cited by 35 publications

(45 citation statements)

References 112 publications

(131 reference statements)

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“…Other members of the chitinase family, such as chitinase-3-like protein 1 (CHI3L1) or chitinase-3-like protein 2 (CHI3L2), bind chitin but do not exhibit enzymatic activity 11. Recent evidence implicates chitinases in regulating the innate immune system12 and modulating inflammation during the progression of many diseases 13. Given that chitinases are expressed by activated microglia and/or astrocytes in the central nervous system (CNS), these biomarkers may be reflective of glial activation.…”

Section: Introductionmentioning

confidence: 99%

Cross-sectional and longitudinal measures of chitinase proteins in amyotrophic lateral sclerosis and expression of CHI3L1 in activated astrocytes

Kovalik

et al. 2020

J Neurol Neurosurg Psychiatry

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ObjectiveAmyotrophic lateral sclerosis (ALS) is a complex disease with numerous pathological mechanisms resulting in a heterogeneous patient population. Using biomarkers for particular disease mechanisms may enrich a homogeneous subset of patients. In this study, we quantified chitotriosidase (Chit-1) and chitinase-3-like protein 1 (CHI3L1), markers of glial activation, in cerebrospinal fluid (CSF) and plasma and determined the cell types that express CHI3L1 in ALS.MethodsImmunoassays were used to quantify Chit-1, CHI3L1 and phosphorylated neurofilament heavy chain levels in longitudinal CSF and matching plasma samples from 118 patients with ALS, 17 disease controls (DCs), and 24 healthy controls (HCs). Immunostaining was performed to identify and quantify CHI3L1-positive cells in tissue sections from ALS, DCs and non-neurological DCs.ResultsCSF Chit-1 exhibited increased levels in ALS as compared with DCs and HCs. CSF CHI3L1 levels were increased in ALS and DCs compared with HCs. No quantitative differences were noted in plasma for either chitinase. Patients with ALS with fast-progressing disease exhibited higher levels of CSF Chit-1 and CHI3L1 than patients with slow-progressing disease. Increased numbers of CHI3L1-positive cells were observed in postmortem ALS motor cortex as compared with controls, and these cells were identified as a subset of activated astrocytes located predominately in the white matter of the motor cortex and the spinal cord.ConclusionsCSF Chit-1 and CHI3L1 are significantly increased in ALS, and CSF Chit-1 and CHI3L1 levels correlate to the rate of disease progression. CHI3L1 is expressed by a subset of activated astrocytes predominately located in white matter.

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Section: Introductionmentioning

confidence: 99%

Cross-sectional and longitudinal measures of chitinase proteins in amyotrophic lateral sclerosis and expression of CHI3L1 in activated astrocytes

Kovalik

et al. 2020

J Neurol Neurosurg Psychiatry

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“…Chil3 (also known as YKL-40 in humans and BRP-39 in mice) does not contain known chitinase activity, though it has been implicated in host defense, inflammation, and remodeling processes 73,74 . Chil3 has been reported as a biomarker for skin wound infection 96 , cardiovascular disease and diabetes 97 , and cancer 98 .…”

Section: Discussionmentioning

confidence: 99%

“…Chil3 is a member of the mammalian chitinase family that lacks the chitinase activity though it is highly secreted by macrophages and neutrophils 71,72 . Similar to the function of S100 proteins, chitinase-like proteins have also been shown to be mediators of inflammation and antimicrobial responses in multiple models of disease such as asthma and pulmonary fibrosis as well as involved in tissue remodeling and wound healing [73][74][75] . In previous work in kidney disease models, a urinary proteomic study has shown that chitinases-like proteins could be candidate biomarkers for S-AKI 75 .…”

Section: Discovery-based Studies Recapitulate Signature Proteins For mentioning

confidence: 99%

The global proteome and phosphoproteome landscape of sepsis-induced kidney injury

Lin

Platt

Zhou

et al. 2020

Preprint

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Sepsis-induced acute kidney injury (S-AKI) is the most common complication in hospitalized and critically ill patients, highlighted by a rapid decline of kidney function occurring a few hours or days after sepsis onset. Systemic inflammation elicited by microbial infections is believed to lead to kidney damage under immunocompromised conditions. However, while AKI has been recognized as a disease with long-term sequelae, partly due to the associated higher risk of chronic kidney disease (CKD), the understanding of kidney pathophysiology at the molecular level and the global view of dynamic regulations in situ after S-AKI, including transition to CKD, remains limited. Existing studies of S-AKI mainly focus on deriving sepsis biomarkers from body fluids. In the present study, we constructed a mid-severity septic murine model using cecal ligation and puncture (CLP), and examined the temporal changes to the kidney proteome and phosphoproteome at day 2 and day 7 after CLP surgery, corresponding to S-AKI and the transition to CKD, respectively by employing an ultrafast and economical filter-based sample processing method combined with the label-free quantitation approach. Collectively, we identified 2,119 proteins and 2,950 phosphosites through multi-proteomics analyses. Here we denote the pathways that are specifically responsive to S-AKI and its transition to CKD, which include regulation of cell metabolism regulation, oxidative stress, and energy consumption in the diseased kidneys. Our data can serve as an enriched resource for the identification of mechanisms and biomarkers for sepsis-induced kidney diseases.

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“…Elevated levels of CHI3L1 and CHI3L2 have been shown to drive proliferation of a number of human cells (28,30,32,33,42) and are associated with numerous chronic inflammatory diseases (e.g. arthritis and asthma (43)(44)(45) and poor prognosis of several cancers including glioblastoma, nonsmall-cell lung cancer and colorectal cancer (46)(47)(48)(49)(50). Interestingly, in the case of colorectal cancer, downregulation of DIS3L2 (as a consequence of knockdown of lncRNA AC105461.1) enhances the proliferation and stem-cell like properties of cells of the colorectal cancer line SW480 (51).…”

Section: Idgf2 Is a Conserved Member Of The Chitinase-like Family Witmentioning

confidence: 99%

Dis3L2 regulates cellular proliferation through a PI3-Kinase dependent signalling pathway

Towler

Pashler

Haime

et al. 2019

Preprint

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Dis3L2 is a highly conserved 3'-5' exoribonuclease which is mutated in the human overgrowth disorders Perlman syndrome and Wilms' tumour. Here, we have generated a new dis3L2 null mutant and a UAS-nuclease-dead line in Drosophila to demonstrate that the catalytic activity of Dis3L2 is required to control proliferation in imaginal discs. Using RNA-seq on dis3L2 mutant wing discs, we show that the imaginal disc growth factor Idgf2 is responsible for driving the wing overgrowth observed in dis3L2 null mutants. IDGFs are conserved proteins homologous to human chitinase-like proteins such as CHI3L1/YKL-40 which are implicated in tissue regeneration as well as cancers including colon cancer and non-small cell lung cancer. We also show that loss of DIS3L2 in human HEK-293T cells results in cell proliferation, illustrating the conservation of this important cell proliferation pathway. Using these human cells we show that loss of DIS3L2 results in an increase in the activity of the PI3-Kinase/AKT signalling pathway, which we subsequently show to also have a role in driving the proliferation phenotype in Drosophila. Our work therefore provides the first mechanistic explanation for DIS3L2-induced overgrowth in humans and flies and identifies an ancient proliferation pathway controlled by Dis3L2 to regulate cell proliferation and tissue growth.

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Chitinase-like proteins as regulators of innate immunity and tissue repair: helpful lessons for asthma?

Cited by 35 publications

References 112 publications

Cross-sectional and longitudinal measures of chitinase proteins in amyotrophic lateral sclerosis and expression of CHI3L1 in activated astrocytes

Cross-sectional and longitudinal measures of chitinase proteins in amyotrophic lateral sclerosis and expression of CHI3L1 in activated astrocytes

The global proteome and phosphoproteome landscape of sepsis-induced kidney injury

Dis3L2 regulates cellular proliferation through a PI3-Kinase dependent signalling pathway

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