Relationship between YKL-40 and pulmonary arterial hypertension in systemic sclerosis

Furukawa, T.; Kitano, Masayasu; Yokoyama, Yuichi; Sekiguchi, Mutsuo; Azuma, Naoto; Imai, Yasutomo; Hirota, Seiichi; Yamanishi, Kiyofumi; Sano, Hajime

doi:10.1080/14397595.2018.1480256

Cited by 13 publications

(7 citation statements)

References 28 publications

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“…Our finding of increased serum YKL-40 concentrations in IPF compared with controls is in complete agreement with the previous clinical research studies in the ILD field reporting elevated YKL-40 concentrations in serum and/or BALf of patients with IPF (27)(28)(29)(30), sarcoidosis (44,45), or connective tissue disease-associated ILD (CTD-ILD) (29,(46)(47)(48)(49). It has been also shown that high serum and BALf YKL-40 concentrations are associated with poor survival in patients with IPF and hypersensitivity pneumonitis (HP) (28,30).…”

Section: Longitudinal Changes Insupporting

confidence: 92%

Longitudinal and Comparative Measures of Serum Chitotriosidase and YKL-40 in Patients With Idiopathic Pulmonary Fibrosis

et al. 2022

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BackgroundAlthough chitin is absent in humans, chitinases are present in healthy subjects and show dysregulated expression in a variety of diseases resulting from abnormal tissue injury and repair responses. It was shown that chitotriosidase (chitinase 1/CHIT1) and structurally-related chitinase 3-like 1 protein (CHI3L1/YKL-40) play important roles in the pathobiology of idiopathic pulmonary fibrosis (IPF), however little is known about their longitudinal serum levels and relationship to clinical measures in IPF.MethodsThe present study is the first to evaluate serial measurements of serum CHIT1 activity and YKL-40 concentrations in patients with IPF starting antifibrotic treatment and followed up for 24 months. In addition, baseline serum CHIT1 and YKL-40 were compared between patients with IPF and control subjects, and possible CHIT1 and YKL-40 relationships to longitudinal clinical assessments in IPF were explored.ResultsBaseline serum CHIT1 activity and YKL-40 concentrations were significantly elevated in patients with IPF compared to control subjects and showed similar discriminatory ability in distinguishing IPF from controls. No significant differences between the median serum CHIT1 activity and YKL-40 concentration measured over a study follow-up were noted. We found significantly elevated baseline serum CHIT1 activity in the progressors compared with the stables in the first year, while significantly increased baseline serum CHIT1 activity was noted in the stables compared to the progressors in the second year. Additionally, we observed a significant negative correlation between a change in serum YKL-40 concentration and a change in forced vital capacity (FVC) % predicted (% pred.) in the stables subgroup, whereas, a change in serum CHIT1 activity correlated negatively with a change in FVC% pred. in the progressors subgroup.ConclusionsThis explorative study findings add further evidence that CHIT1 and YKL-40 are upregulated in patients with IPF, and suggest that longitudinally stable serum CHIT1 activity and YKL-40 concentration levels may potentially be associated with the antifibrotic treatment response. In addition, our findings are supporting the possible role of CHIT1 and YKL-40 as candidate diagnostic and prognostic biomarkers in IPF. Further research is needed to validate present study findings.

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Section: Longitudinal Changes Insupporting

confidence: 92%

Longitudinal and Comparative Measures of Serum Chitotriosidase and YKL-40 in Patients With Idiopathic Pulmonary Fibrosis

et al. 2022

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“…Previous studies have identified CHI3L1 as an indicator of disease severity and prognosis in patients with IPAH (21), PAH associated with scleroderma (22), and IPF (19), but the mechanism of CHI3L1 in the pathogenesis of PH has not been investigated. The importance of CHI3L1induced responses can be seen in the large number of diseases characterized by inflammation and remodeling in which CHI3L1 excess has been documented (52)(53)(54)(55)(56)(57)(58)(59)(60).…”

Section: Discussionmentioning

confidence: 99%

Chitinase 3 like 1 contributes to the development of pulmonary vascular remodeling in pulmonary hypertension

et al. 2022

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Chitinase 3-like 1 (CHI3L1) is the prototypic chitinase-like protein mediating inflammation, cell proliferation, and tissue remodeling. Limited data suggests CHI3L1 is elevated in human pulmonary arterial hypertension (PAH) and is associated with disease severity. Despite its importance as a regulator of injury/repair responses, the relationship between CHI3L1 and pulmonary vascular remodeling is not well understood. We hypothesize that CHI3L1 and its signaling pathways contribute to the vascular remodeling responses that occur in pulmonary hypertension (PH). We examined the relationship of plasma CHI3L1 levels and severity of PH in patients with various forms of PH, including Group 1 PAH and Group 3 PH, and found that circulating levels of serum CHI3L1 were associated with worse hemodynamics and correlated directly with mean pulmonary artery pressure and pulmonary vascular resistance. We also used transgenic mice with constitutive knockout and inducible overexpression of CHI3L1 to examine its role in hypoxia-, monocrotaline-, and bleomycin-induced models of pulmonary vascular disease.In all 3 mouse models of pulmonary vascular disease, pulmonary hypertensive responses were mitigated in CHI3L1 null mice and accentuated in transgenic mice that overexpress CHI3L1.Finally, CHI3L1 alone was sufficient to induce pulmonary arterial smooth muscle cell proliferation, inhibit pulmonary vascular endothelial cell apoptosis, induce the loss of endothelial barrier function, and induce endothelial-to-mesenchymal transition. These findings demonstrate that CHI3L1 and its receptors play an integral role in pulmonary vascular disease pathobiology and may offer a novel target for the treatment PAH and PH associated with fibrotic lung disease.

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“…In addition, in a cohort of 64 IPF patients and 42 age-matched controls, CHI3L1 levels were elevated in patients with IPF, and high levels of CHI3L1 are associated with severe disease progression as defined by lung transplantation or death ( Zhou et al, 2014 ). Since then, numerus studies have showed that the serum CHI3L1 levels are increased in patients with other types of ILD, including connective tissue-related ILD ( Hozumi et al, 2017 ; Furukawa et al, 2019 ; Jiang et al, 2019 ), sarcoidosis ( Johansen et al, 2005 ; Kruit et al, 2007 ), cryptogenic tissue pneumonia ( Korthagen et al, 2014 ; Long et al, 2017 ), asbestosis-ILD ( Väänänen et al, 2017 ), and idiopathic nonspecific interstitial ( Korthagen et al, 2014 ; Long et al, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

Targeting Chitinase 1 and Chitinase 3-Like 1 as Novel Therapeutic Strategy of Pulmonary Fibrosis

Lee

Kamle

et al. 2022

Front. Pharmacol.

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Chitinase 1 (CHIT1) and chitinase 3-like-1 (CHI3L1), two representative members of 18-Glycosyl hydrolases family, are significantly implicated in the pathogenesis of various human diseases characterized by inflammation and remodeling. Notably, dysregulated expression of CHIT1 and CHI3L1 was noted in the patients with pulmonary fibrosis and their levels were inversely correlated with clinical outcome of the patients. CHIT1 and CHI3L1, mainly expressed in alveolar macrophages, regulate profibrotic macrophage activation, fibroblast proliferation and myofibroblast transformation, and TGF-β signaling and effector function. Although the mechanism or the pathways that CHIT1 and CHI3L1 use to regulate pulmonary fibrosis have not been fully understood yet, these studies identify CHIT1 and CHI3L1 as significant modulators of fibroproliferative responses leading to persistent and progressive pulmonary fibrosis. These studies suggest a possibility that CHIT1 and CHI3L1 could be reasonable therapeutic targets to intervene or reverse established pulmonary fibrosis. In this review, we will discuss specific roles and regulatory mechanisms of CHIT1 and CHI3L1 in profibrotic cell and tissue responses as novel therapeutic targets of pulmonary fibrosis.

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Relationship between YKL-40 and pulmonary arterial hypertension in systemic sclerosis

Abstract: A higher YKL-40 level with PAH may be reflective of angiogenesis due to capillary injury in SSc. YKL-40 may offer a useful and easily applicable diagnostic biomarker of SSc complicated with PAH.

Cited by 13 publications

References 28 publications

Longitudinal and Comparative Measures of Serum Chitotriosidase and YKL-40 in Patients With Idiopathic Pulmonary Fibrosis

Longitudinal and Comparative Measures of Serum Chitotriosidase and YKL-40 in Patients With Idiopathic Pulmonary Fibrosis

Chitinase 3 like 1 contributes to the development of pulmonary vascular remodeling in pulmonary hypertension

Targeting Chitinase 1 and Chitinase 3-Like 1 as Novel Therapeutic Strategy of Pulmonary Fibrosis

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