Effects of chitinase-1 inhibitor in obesity-induced and -aggravated asthma in a murine model

Han, Heejae; Choi, Yong Jun; Hong, Hyerim; Kim, Chi Young; Byun, Min Kwang; Cho, Jae Hwa; Lee, Jae-Hyun; Park, Jung-Won; Doherty, Taylor A.; Park, Hye Jung

doi:10.1016/j.lfs.2023.122163

Cited by 3 publications

(1 citation statement)

References 34 publications

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“…Dietary approaches like high-fat diets (HFD) have been implicated in increasing in ammation and oxidative stress, whereas agents like pentamidine-liked bisindole may activate anti-in ammatory pathways, such as AMPK, offering therapeutic relief in obesity-related asthma [15]. Moreover, novel pharmacological treatments like CPX (carnosine-phenylalanine-boron) and FFA4 activators are being explored for their e cacy in treating obesity-aggravated asthma, particularly by preventing airway remodeling and brosis [21,22].…”

Section: Discussionmentioning

confidence: 99%

Variation of all-cause mortality with Fat-free Mass Index（FFMI）and Fat Mass Index（FMI）in individuals with Asthma: results from the NHANES database prospective cohort study

Chen,

Cheng,

Yao

et al. 2024

Preprint

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Background The relationship between FFMI, FMI, and mortality in patients with asthma remains unknown. This study aimed to examine the associations between FFMI and FMI and all-cause mortality in a cohort of American adults diagnosed with asthma. Methods This study included 15200 adults from NHANES. To assess mortality, we linked participant records to the National Death Index. Survival differences across quintiles of FFMI and FMI were explored using Kaplan-Meier plots and log-rank tests. The study investigated the nonlinear relationships between FFMI, FMI, and mortality. Additionally, stratified analyses were undertaken to pinpoint subgroups of individuals who exhibited an elevated risk of mortality. Results After a median follow-up, 13360 were presumed alive and 1840 had deceased. Kaplan-Meier plots revealed significant differences in all-cause mortality in patients with asthma among the FFMI quintiles and FMI quintiles. Specifically, individuals in the lowest FFMI quintile (Q1, 10.4-16.0) exhibited a markedly increased risk of all-cause mortality (HR: 4.63; 95% CI: 1.59,13.5; p< 0.01). Similarly, increased all-cause mortality risks were observed in the upper three quintiles of FMI-Q3 (4.8-6.1) with HR: 2.9 (1.20,7.00, p<0.05), Q4 (6.2-8.3) with HR: 3.37 (1.41,8.03, p<0.01), and Q5 (8.4-22.8) with HR: 4.6 (1.31,16.2, p<0.05). Moreover, the risk of all-cause mortality increased with increasing FMI and decreasing FFMI (p for non-linearity<0.001 in both cases) respectively. Subgroup analyses further elucidated these associations across different categories. Conclusions All-cause mortality is decreased in patients with asthma when FMI is less than 5.4 kg/m2, and increased when FFMI is less than 18.6 kg/m2.

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Section: Discussionmentioning

confidence: 99%

Variation of all-cause mortality with Fat-free Mass Index（FFMI）and Fat Mass Index（FMI）in individuals with Asthma: results from the NHANES database prospective cohort study

Chen,

Cheng,

Yao

et al. 2024

Preprint

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Long-term alterations in lung epithelial cells after EL-RSV infection exacerbate allergic responses through IL-1β-induced pathways

Morris,

Ocadiz-Ruiz,

Asai

et al. 2024

Mucosal Immunology

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Chitinase 1: a novel therapeutic target in metabolic dysfunction-associated steatohepatitis

Cha,

Park,

Cho

et al. 2024

Front. Immunol.

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BackgroundMetabolic dysfunction-associated steatohepatitis (MASH) is characterized by persistent inflammatory cascades, with macrophage activation playing a pivotal role. Chitinase 1 (CHIT1), produced by activated macrophages, is a key player in this cascade. In this study, we aimed to explore the role of CHIT1 in MASH with progressive liver fibrosis.MethodsFibrotic liver tissue and serum from distinct patient groups were analyzed using nCounter MAX, flow cytometry, immunohistochemistry, and enzyme-linked immunosorbent assay. A MASH mouse model was constructed to evaluate the effectiveness of OATD-01, a chitinase inhibitor. Macrophage profiling was performed using single-nuclei RNA sequencing and flow cytometry.ResultsCHIT1 expression in fibrotic liver tissues was significantly correlated with the extent of liver fibrosis, macrophages, and inflammation. Single-nuclei RNA sequencing demonstrated a notable increase in macrophages numbers, particularly of lipid-associated macrophages, in MASH mice. Treatment with OATD-01 reduced non-alcoholic fatty liver disease activity score and Sirius red-positive area. Additionally, OATD-01-treated mice had lower CHIT1, F4/80, and α-smooth muscle actin positivity, as well as significantly lower levels of inflammatory markers, pro-fibrotic genes, and matrix remodeling-related mRNAs than vehicle-treated mice. Although the population of F4/80+CD11b+ intrahepatic mononuclear phagocytes remained unchanged, their infiltration and activation (CHIT1+MerTK+) significantly decreased in OATD-01-treated mice, compared with that observed in vehicle-treated mice.ConclusionsOur study underscores the pivotal role of CHIT1 in MASH. The observed significant improvement in inflammation and hepatic fibrosis, particularly at higher doses of the CHIT1 inhibitor, strongly suggests the potential of CHIT1 as a therapeutic target in MASH accompanied by progressive liver fibrosis.

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Effects of chitinase-1 inhibitor in obesity-induced and -aggravated asthma in a murine model

Cited by 3 publications

References 34 publications

Variation of all-cause mortality with Fat-free Mass Index（FFMI）and Fat Mass Index（FMI）in individuals with Asthma: results from the NHANES database prospective cohort study

Variation of all-cause mortality with Fat-free Mass Index（FFMI）and Fat Mass Index（FMI）in individuals with Asthma: results from the NHANES database prospective cohort study

Long-term alterations in lung epithelial cells after EL-RSV infection exacerbate allergic responses through IL-1β-induced pathways

Chitinase 1: a novel therapeutic target in metabolic dysfunction-associated steatohepatitis

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