Role of genetic variations of chitinase 3-like 1 in bronchial asthmatic patients

Abe, Kazuyuki; Nakamura, Yutaka; Yamauchi, Kohei; Maemondo, Makoto

doi:10.1186/s12948-018-0086-7

Cited by 8 publications

(7 citation statements)

References 29 publications

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“…The same associations were replicated in Japanese asthmatics, in whom the CHI3L1 SNP rs12141494 AA genotype was associated with decreased FEV1% 33. Furthermore, the CHI3L1 SNP rs12141494 A allele was associated with higher levels of YKL-40 in the asthmatic airway as measured in both sputum ( P ≤ 0.05)32 and bronchoalveolar lavage (BAL) ( P < 0.05, 770.8 pg/mL for AA vs. 179.3 pg/mL for GG) 33. These findings suggested that CHI3L1 genetic polymorphism modulated expression of YKL-40 in the airway and contributed to lung function in asthma.…”

Section: Genes Regulating Decline In Lung Function And/or Airway Remomentioning

confidence: 61%

“…The CHI3L1 SNP rs12141494 A allele was significantly associated with higher serum YKL-40 levels and decreased post-bronchodilator FEV1% in the Severe Asthma Research Program cohort 32. The same associations were replicated in Japanese asthmatics, in whom the CHI3L1 SNP rs12141494 AA genotype was associated with decreased FEV1% 33. Furthermore, the CHI3L1 SNP rs12141494 A allele was associated with higher levels of YKL-40 in the asthmatic airway as measured in both sputum ( P ≤ 0.05)32 and bronchoalveolar lavage (BAL) ( P < 0.05, 770.8 pg/mL for AA vs. 179.3 pg/mL for GG) 33.…”

Section: Genes Regulating Decline In Lung Function And/or Airway Remomentioning

confidence: 63%

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Genes and Pathways Regulating Decline in Lung Function and Airway Remodeling in Asthma

Hur

Broide

2019

Allergy Asthma Immunol Res

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Asthma is a common disorder of the airways characterized by airway inflammation and by decline in lung function and airway remodeling in a subset of asthmatics. Airway remodeling is characterized by structural changes which include airway smooth muscle hypertrophy/hyperplasia, subepithelial fibrosis due to thickening of the reticular basement membrane, mucus metaplasia of the epithelium, and angiogenesis. Epidemiologic studies suggest that both genetic and environmental factors may contribute to decline in lung function and airway remodeling in a subset of asthmatics. Environmental factors include respiratory viral infection-triggered asthma exacerbations, and tobacco smoke. There is also evidence that several asthma candidate genes may contribute to decline in lung function, including ADAM33 , PLAUR, VEGF , IL13 , CHI3L1 , TSLP , GSDMB , TGFB1 , POSTN , ESR1 and ARG2 . In addition, mediators or cytokines, including cysteinyl leukotrienes, matrix metallopeptidase-9, interleukin-33 and eosinophil expression of transforming growth factor-β, may contribute to airway remodeling in asthma. Although increased airway smooth muscle is associated with reduced lung function ( i.e. forced expiratory volume in 1 second) in asthma, there have been few long-term studies to determine how individual pathologic features of airway remodeling contribute to decline in lung function in asthma. Clinical studies with inhibitors of individual gene products, cytokines or mediators are needed in asthmatic patients to identify their individual role in decline in lung function and/or airway remodeling.

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Section: Genes Regulating Decline In Lung Function And/or Airway Remomentioning

confidence: 61%

Section: Genes Regulating Decline In Lung Function And/or Airway Remomentioning

confidence: 63%

Genes and Pathways Regulating Decline in Lung Function and Airway Remodeling in Asthma

Hur

Broide

2019

Allergy Asthma Immunol Res

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“…Chitinase 3-like-1 (Chi3L1), also called a breast regression protein 39 (BRP-39) in mouse and YKL-40 in human, is known as a secreted glycoprotein and prototypic mammalian chitinase like protein [11,12]. Increased expression of Chi3L1 protein and mRNA have been shown in various disease models and states including rheumatoid arthritis schizophrenics, inflammatory bowel disease, chronic obstructive pulmonary disease, asthma, diabetes, and atherosclerosis [13][14][15][16][17][18][19], Especially, Chi3L1 expression has been found in a variety of cancer cells such as breast, lung, prostate, colon, rectum, ovary, kidney, breast, glioblastomas, and malignant melanoma [20][21][22][23][24][25][26].…”

Section: Introductionmentioning

confidence: 99%

Chitinase 3 like 1 suppresses the stability and activity of p53 to promote lung tumorigenesis

et al. 2020

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Background: Chitinase 3 like 1 protein (Chi3L1) is expressed in several cancers, and a few evidences suggest that the secreted Chi3L1 contributes to tumor development. However, the molecular mechanisms of intracellular Chi3L1 are unknown in the lung tumor development. Methods: In the present study, we generated Chi3L1 knockout mice (Chi3L1 KO(−/−) ) using CRISPR/Cas9 system to investigate the role of Chi3L1 on lung tumorigenesis. Results:We established lung metastasis induced by i.v. injections of B16F10 in Chi3L1 KO(−/−) . The lung tumor nodules were significantly reduced in Chi3L1 KO(−/−) and protein levels of p53, p21, BAX, and cleaved-caspase 3 were significantly increased in Chi3L1 KO(−/−) , while protein levels of cyclin E1, CDK2, and phsphorylation of STAT3 were decreased in Chi3L1 KO(−/−) . Allograft mice inoculated with B16F10 also suppressed tumor growth and increased p53 and its target proteins including p21 and BAX. In addition, knockdown of Chi3L1 in lung cancer cells inhibited lung cancer cell growth and upregulated p53 expression with p21 and BAX, and a decrease in phosphorylation of STAT3. Furthermore, we found that intracellular Chi3L1 physically interacted and colocalized with p53 to inhibit its protein stability and transcriptional activity for target genes related with cell cycle arrest and apoptosis. In lung tumor patient, we clinically found that Chi3L1 expression was upregulated with a decrease in p53 expression, as well as we validated that intracellular Chi3L1 was colocalized, reversely expressed, and physically interacted with p53, which results in suppression of the expression and function of p53 in lung tumor patient.Conclusions: Our studies suggest that intracellular Chi3L1 plays a critical role in the lung tumorigenesis by regulating its novel target protein, p53 in both an in vitro and in vivo system.

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“…Among the most studied SNPs in the CHI3L1 gene such as rs1538372 or rs10399931, we decided to choose -131 C→G (rs4950928) SNP as it is located in the promoter region of CHI3L1 gene. Besides, there was a growing number of papers reporting its association with asthma in different populations [28][29][30][31][32][33]. These papers are summarized and presented in Table 3.…”

Section: Discussionmentioning

confidence: 99%

Investigation of Chitinase3like-1 (Chiti3L1) Gene Polymorphism (rs4950928) with Susceptibility to Allergic Asthma in Iranian Northwestern Azeri Population

et al. 2019

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Background: In addition to cellular and molecular mechanisms involved in the pathogenesis of asthma, mounting evidence demonstrates the role of Single Nucleotide Polymorphisms (SNPs) in asthma relevant genes conferring susceptibility to the disease. A variety of cells, including airway epithelial cells, neutrophils, and macrophages, produce and release Chitinase-3-Like-1 (CHI3L1) via an IL-13 related pathway. CHI3L1 contributes to tissue remodeling during asthma. The present study aimed to investigate the possible association of rs4950928 SNP in the CHI3L1 gene with a predisposition to allergic asthma in the Iranian Northwestern Azeri population. Materials and Methods: The frequencies of genotypes and alleles of rs4950928 SNP in the CHI3L1 gene were determined with the TaqMan genotyping method in 190 patients with asthma and 190 healthy controls. Results: Genotype analyzing showed that CC genotype is more frequent among the case group (68.4%) vs. in the control group (57.9%), while the GG genotype is more abundant among the control group (7.9%) vs. in the case group (3.2%). Patients with asthma were mostly found to have C allele whereas most of the healthy individuals had G allele in their genotype. Conclusion: There is a significant relationship between CHI3L1 rs4950928 (-131 C/G) polymorphism and asthma in studied population (P=0.038, P<0.05). Furthermore, according to the odds ratio (case/ control =0.611), the C allele could be the risk allele, whereas the G allele can be the protective one.

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Role of genetic variations of chitinase 3-like 1 in bronchial asthmatic patients

Cited by 8 publications

References 29 publications

Genes and Pathways Regulating Decline in Lung Function and Airway Remodeling in Asthma

Genes and Pathways Regulating Decline in Lung Function and Airway Remodeling in Asthma

Chitinase 3 like 1 suppresses the stability and activity of p53 to promote lung tumorigenesis

Investigation of Chitinase3like-1 (Chiti3L1) Gene Polymorphism (rs4950928) with Susceptibility to Allergic Asthma in Iranian Northwestern Azeri Population

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