Genetic variations in the Wnt signaling pathway affect lung function in asthma patients

Sh, Wang; Fang, Xu; Hx, Dang; Yang, Linjun

doi:10.4238/2013.january.4.1

Cited by 13 publications

(9 citation statements)

References 14 publications

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“… 25 Consistent with this study, another genetic study, in an adult population, found a significant association between a single nucleotide polymorphism of the Wnt-1-induced secreted protein 1 gene and lung function in Chinese adults with asthma. 26 These findings support that Wnt/β-catenin signaling is involved in asthma and has roles in Th2 inflammation and the decline in lung function. In line with these reports, we provide the first evidence that the Wnt/β-catenin signaling pathway is highly upregulated in the asthmatic airway in vivo by showing high Wnt7a expression in the induced sputum from patients with asthma.…”

Section: Discussionsupporting

confidence: 57%

The Wnt/β-catenin signaling pathway regulates the development of airway remodeling in patients with asthma

et al. 2015

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Airway remodeling is a key characteristic of chronic asthma, particularly in patients with a fixed airflow limitation. The mechanisms underlying airway remodeling are poorly understood, and no therapeutic option is available. The Wnt/β-catenin signaling pathway is involved in various physiological and pathological processes, including fibrosis and smooth muscle hypertrophy. In this study, we investigated the roles of Wnt/β-catenin signaling in airway remodeling in patients with asthma. Wnt7a mRNA expression was prominent in induced sputum from patients with asthma compared with that from healthy controls. Next, we induced a chronic asthma mouse model with airway remodeling features, including subepithelial fibrosis and airway smooth muscle hyperplasia. Higher expression of Wnt family proteins and β-catenin was detected in the lung tissue of mice with chronic asthma compared to control mice. Blocking β-catenin expression with a specific siRNA attenuated airway inflammation and airway remodeling. Decreased subepithelial fibrosis and collagen accumulation in the β-catenin siRNA-treated mice was accompanied by reduced expression of transforming growth factor-β. We further showed that suppressing β-catenin in the chronic asthma model inhibited smooth muscle hyperplasia by downregulating the tenascin C/platelet-derived growth factor receptor pathway. Taken together, these findings demonstrate that the Wnt/β-catenin signaling pathway is highly expressed and regulates the development of airway remodeling in chronic asthma.

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Section: Discussionsupporting

confidence: 57%

The Wnt/β-catenin signaling pathway regulates the development of airway remodeling in patients with asthma

et al. 2015

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“…Furthermore, a single nucleotide polymorphism (SNP; rs2929973) in the WISP1 gene is significantly associated with FEV 1 in asthmatic children, whereas an SNP in WIF-1 does influence lung function (ie, FEV 1 ). 85 Moreover, a recent publication, which used a genome-wide association study (GWAS)-based analysis to prioritise asthma susceptibility genes, revealed two biological pathways to be enriched in asthma pathogenesis: (1) cytokine-cytokine receptor interactions and (2) WNT signalling pathway(s). The same study identified a novel susceptibility locus near WNT signalling genes, in particular SNPs located near FZD3 and FZD6.…”

Section: Wnt Signalling In Asthmamentioning

confidence: 99%

‘WNT-er is coming’: WNT signalling in chronic lung diseases

Baarsma

Königshoff

2017

Thorax

161

138

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Chronic lung diseases represent a major public health problem with only limited therapeutic options. An important unmet need is to identify compounds and drugs that target key molecular pathways involved in the pathogenesis of chronic lung diseases. Over the last decade, there has been extensive interest in investigating Wingless/integrase-1 (WNT) signalling pathways; and WNT signal alterations have been linked to pulmonary disease pathogenesis and progression. Here, we comprehensively review the cumulative evidence for WNT pathway alterations in chronic lung pathologies, including idiopathic pulmonary fibrosis, pulmonary arterial hypertension, asthma and COPD. While many studies have focused on the canonical WNT/β-catenin signalling pathway, recent reports highlight that non-canonical WNT signalling may also significantly contribute to chronic lung pathologies; these studies will be particularly featured in this review. We further discuss recent advances uncovering the role of WNT signalling early in life, the potential of pharmaceutically modulating WNT signalling pathways and highlight (pre)clinical studies describing promising new therapies for chronic lung diseases.

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“…WISP1 rs2929970 was also suggested to be correlated with hypertension in men, and men carrying the G allele of rs2929970 had higher blood pressure [26]. Moreover, WISP1 rs2929973 was associated with lung function in asthmatic children [25]. In lung cancer, a series of WISP1 genetic polymorphisms, such as rs16893344, rs2977530, rs2977537, rs62514004, rs11778573, rs2977536, and rs2977549, were significantly associated with lung cancer susceptibility or the chemotherapy response [22].…”

Section: Introductionmentioning

confidence: 99%

Effect of genetic variation in microRNA binding site in WNT1-inducible signaling pathway protein 1 gene on oral squamous cell carcinoma susceptibility

Lau

Chen

et al. 2017

PLoS ONE

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BackgroundOral squamous cell carcinoma (OSCC), which is the most common head and neck cancer, accounts for 1%–2% of all human malignancies and is characterized by poor prognosis and reduced survival rates. WNT1-inducible signaling pathway protein 1 (WISP1), a cysteine-rich protein belonging to the Cyr61, CTGF, Nov (CCN) family of matricellular proteins, has many developmental functions and may be involved in carcinogenesis. This study investigated WISP1 single-nucleotide polymorphisms (SNPs) to elucidate OSCC susceptibility and clinicopathologic characteristics.Methodology/Principal findingsReal-time polymerase chain reaction was used to analyze 6 SNPs of WISP1 in 900 OSCC patients and 1200 cancer-free controls. The results showed that WISP1 rs2929970 polymorphism carriers with at least one G allele were susceptible to OSCC. Moreover, compared with smokers, non-smoker patients with higher frequencies of WISP1 rs2929970 (AG + GG) variants had a late stage (stages III and IV) and a large tumor size. In addition, OSCC patients who were betel quid chewers and carried WISP1 rs16893344 (CT + TT) variants had a low risk of lymph node metastasis.ConclusionOur results demonstrate that a joint effect of WISP1 rs2929970 with smoking as well as WISP1 rs16893344 with betel nut chewing causally contributes to the occurrence of OSCC. WISP1 polymorphism may serve as a marker or a therapeutic target in OSCC.

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Genetic variations in the Wnt signaling pathway affect lung function in asthma patients

Cited by 13 publications

References 14 publications

The Wnt/β-catenin signaling pathway regulates the development of airway remodeling in patients with asthma

The Wnt/β-catenin signaling pathway regulates the development of airway remodeling in patients with asthma

‘WNT-er is coming’: WNT signalling in chronic lung diseases

Effect of genetic variation in microRNA binding site in WNT1-inducible signaling pathway protein 1 gene on oral squamous cell carcinoma susceptibility

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