The Role of Secreted Frizzled-related Protein-1 in Allergic Asthma

Rai, Nooralam; Arteaga‐Solis, Emilio; Goldklang, Monica; Zelonina, Tina; DʼArmiento, Jeanine

doi:10.1165/rcmb.2020-0314oc

Cited by 4 publications

(4 citation statements)

References 35 publications

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“…Using bronchial epithelium samples from patients with asthma, Hachim et al [42 ▪ ] observed that a Th2 high phenotype was associated with upregulation of Wnt inhibitory modulators. Consistent with this, our group demonstrated that SFRP-1, an endogenous protein that binds to Frizzled receptors and inhibits Wnt ligand binding, potentiates allergic asthma in a house dust mite mouse model, and genetic ablation of Sfrp-1 led to reduced alternatively activated alveolar macrophages compared to wild type mice [43]. Dickkopf-1 (DKK-1), a Wnt antagonist, promoted polarization of T cells into Th2 cells, and its functional inhibition in a house dust mite asthma model was protective [44].…”

Section: Wingless/integrase-1 and Allergic Asthmasupporting

confidence: 63%

Wingless/integrase-1 signaling in allergic asthma and pediatric lung diseases

Rai¹,

DʼArmiento

2022

Current Opinion in Pediatrics

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Purpose of reviewTo provide an update on the current understanding of the role of wingless/integrase-1 (Wnt) signaling in pediatric allergic asthma and other pediatric lung diseases.Recent findingsThe Wnt signaling pathway is critical for normal lung development. Genetic and epigenetic human studies indicate a link between Wnt signaling and the development and severity of asthma in children. Mechanistic studies using animal models of allergic asthma demonstrate a key role for Wnt signaling in allergic airway inflammation and remodeling. More recently, data on bronchopulmonary dysplasia (BPD) pathogenesis points to the Wnt signaling pathway as an important regulator.SummaryCurrent data indicates that the Wnt signaling pathway is an important mediator in allergic asthma and BPD pathogenesis. Further studies are needed to characterize the roles of individual Wnt signals in childhood disease, and to identify potential novel therapeutic targets to slow or prevent disease processes.

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Section: Wingless/integrase-1 and Allergic Asthmasupporting

confidence: 63%

Wingless/integrase-1 signaling in allergic asthma and pediatric lung diseases

Rai¹,

DʼArmiento

2022

Current Opinion in Pediatrics

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“…As such, the reduced levels of stromal SFRP1 and SFRP2 in DCIS and IDC may facilitate WNT signaling and promote breast cancer growth, survival, invasion, or stem cell activity. SFRPs may also enhance tumor angiogenesis through non-canonical WNT signaling ( 59 ) and regulating macrophage recruitment during inflammation ( 70 ). As such, SFRP1 and SFRP2 expression in fibroblasts could serve to regulate breast cancer progression by acting on epithelial cells and other cells in the tumor microenvironment.…”

Section: Discussionmentioning

confidence: 99%

Transcriptome analysis reveals differences in cell cycle, growth and migration related genes that distinguish fibroblasts derived from pre-invasive and invasive breast cancer

et al. 2023

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Background/IntroductionAs the most common form of pre-invasive breast cancer, ductal carcinoma in situ (DCIS) affects over 50,000 women in the US annually. Despite standardized treatment involving lumpectomy and radiation therapy, up to 25% of patients with DCIS experience disease recurrence often with invasive ductal carcinoma (IDC), indicating that a subset of patients may be under-treated. As most DCIS cases will not progress to invasion, many patients may experience over-treatment. By understanding the underlying processes associated with DCIS to IDC progression, we can identify new biomarkers to determine which DCIS cases may become invasive and improve treatment for patients. Accumulation of fibroblasts in IDC is associated with disease progression and reduced survival. While fibroblasts have been detected in DCIS, little is understood about their role in DCIS progression.GoalsWe sought to determine 1) whether DCIS fibroblasts were similar or distinct from normal and IDC fibroblasts at the transcriptome level, and 2) the contributions of DCIS fibroblasts to breast cancer progression.MethodsFibroblasts underwent transcriptome profiling and pathway analysis. Significant DCIS fibroblast-associated genes were further analyzed in existing breast cancer mRNA databases and through tissue array immunostaining. Using the sub-renal capsule graft model, fibroblasts from normal breast, DCIS and IDC tissues were co-transplanted with DCIS.com breast cancer cells.ResultsThrough transcriptome profiling, we found that DCIS fibroblasts were characterized by unique alterations in cell cycle and motility related genes such as PKMYT1, TGF-α, SFRP1 and SFRP2, which predicted increased cell growth and invasion by Ingenuity Pathway Analysis. Immunostaining analysis revealed corresponding increases in expression of stromal derived PKMYT1, TGF-α and corresponding decreases in expression of SFRP1 and SFRP2 in DCIS and IDC tissues. Grafting studies in mice revealed that DCIS fibroblasts enhanced breast cancer growth and invasion associated with arginase-1+ cell recruitment.ConclusionDCIS fibroblasts are phenotypically distinct from normal breast and IDC fibroblasts, and play an important role in breast cancer growth, invasion, and recruitment of myeloid cells. These studies provide novel insight into the role of DCIS fibroblasts in breast cancer progression and identify some key biomarkers associated with DCIS progression to IDC, with important clinical implications.

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“…While it is currently well-understood that these structural and functional changes arise from persistent Type 2 inflammation of the airways in response to aeroallergen exposure, the mechanisms responsible for initiating and maintaining eosinophilic inflammation in allergic airway disease remain unclear. Here, Rai et al describe their studies of canonical Wnt signaling pathway and its importance in the regulation of the pulmonary immune response to inhaled allergen, particularly regarding the differentiation and activity of alternatively activated M2 macrophages (1).…”

mentioning

confidence: 99%

“…In this issue of the Journal , Rai and colleagues (pp. 293–301 ) describe their studies of canonical Wnt signaling pathway and its importance in the regulation of the pulmonary immune response to inhaled allergen, particularly regarding the differentiation and activity of alternatively activated M2 macrophages ( 1 ).…”

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confidence: 99%