High serum levels of IGF-I and IGFBP3 may increase comorbidity risk for asthmatic patients

Acat, Murat; Erbay, Umran Toru; Sahin, Şevki; Arık, Özlem; Ayada, Ceylan

doi:10.4149/bll_2017_130

Cited by 8 publications

(7 citation statements)

References 16 publications

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“…HDM-mediated induction of Igf1 could be responsible for IGF1R phosphorylation to promote the asthmatic response, and therefore supports why targeting IGF1R with NVP ameliorates HDM-induced asthma. Accordingly, IGF1 was reported to be involved in airway inflammation and remodeling in asthma and increased in serum of asthmatic patients [ 7 , 13 , 14 , 29 ].…”

Section: Discussionmentioning

confidence: 99%

IGF1R as a Potential Pharmacological Target in Allergic Asthma

et al. 2021

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Background: Asthma is a chronic lung disease characterized by reversible airflow obstruction, airway hyperresponsiveness (AHR), mucus overproduction and inflammation. Although Insulin-like growth factor 1 receptor (IGF1R) was found to be involved in asthma, its pharmacological inhibition has not previously been investigated in this pathology. We aimed to determine if therapeutic targeting of IGF1R ameliorates allergic airway inflammation in a murine model of asthma. Methods: C57BL/6J mice were challenged by house dust mite (HDM) extract or PBS for four weeks and therapeutically treated with the IGF1R tyrosine kinase inhibitor (TKI) NVP-ADW742 (NVP) once allergic phenotype was established. Results: Lungs of HDM-challenged mice exhibited a significant increase in phospho-IGF1R levels, incremented AHR, airway remodeling, eosinophilia and allergic inflammation, as well as altered pulmonary surfactant expression, all of being these parameters counteracted by NVP treatment. HDM-challenged lungs also displayed augmented expression of the IGF1R signaling mediator p-ERK1/2, which was greatly reduced upon treatment with NVP. Conclusions: Our results demonstrate that IGF1R could be considered a potential pharmacological target in murine HDM-induced asthma and a candidate biomarker in allergic asthma.

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Section: Discussionmentioning

confidence: 99%

IGF1R as a Potential Pharmacological Target in Allergic Asthma

et al. 2021

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“…A recent case-control study demonstrated that IGF-1 serum was higher in asthmatics than in control subjects. 11 In contrast, IGF-1 serum was positively associated with lung function in two cross-sectional epidemiological studies in adults, mainly in men, 12,13 although the results do not replicate prospectively. 12 And a recent large cross-sectional study in adults in the UK 14 showed that elevated serum IGF-1 concentration was associated with a low risk of asthma and recent wheezing and improved lung function.…”

Section: Discussionmentioning

confidence: 93%

“…In an in vivo study, IGF‐1 promoted airway inflammation by upregulating IGF‐binding protein 3 (IGFBP‐3), which may have profibrotic effects 10 . A recent case‐control study in adults reported that serum IGF‐1 was higher in asthmatics than in control subjects, but these findings should be interpreted cautiously due to the small sample size 11 . In contrast, IGF‐1 serum was positively associated with lung function in two epidemiological studies in adults, 12,13 and a recent large cross‐sectional study in adults in the UK 14 showed that higher serum IGF‐1 levels were associated with low risk of asthma and recent wheezing and improved lung function (FEV 1 and FVC), suggesting a potential beneficial effect of IGF‐1 on asthma and its parameters in adults.…”

Section: Introductionmentioning

confidence: 99%

Higher levels of insulin‐like growth factor‐1 in cord blood associate with risk of asthma at age 3

Castro‐Rodriguez,

Padilla,

Casanello

et al. 2023

Pediatric Pulmonology

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RationaleExperimental studies and epidemiological data in adults suggest that somatomedin‐C (insulin‐like growth factor‐1, IGF‐1) may play a role in asthma by modulating airway inflammation, bronchial hyperreactivity, and airway smooth muscle hyperplasia. However, its role in children with asthma is not well understood.MethodsWe established a birth cohort with 339 Chilean pregnant mothers enrolled at the time of delivery from December 2014 to January 2016. We obtained cord blood at birth and followed the offspring every 6 months until 30 months of age, recording data on atopy, wheezing, and other respiratory illnesses. We measured IGF‐1 in cord blood and determined the Asthma Predictive Index (API) at 30 months. The cohort was divided according to the API.ResultsComplete data were available for 307/339 (91%) dyads, including 44 preschoolers with API+ and 263 with API–. Demographic characteristics were similar between groups, but mothers of API+ children had a higher prevalence of obesity, previous use of oral contraceptives, and higher education than those of API– children. API+ children had higher birth weight and significantly higher IGF‐1 in cord blood (37.4 ± 13.2 in API+ vs. 30.5 ± 13.0 ng/ml in API–, p = .01). In the multivariable analysis, IGF‐1 in cord blood remained independently associated with a higher risk of asthma (adjusted OR for API+ per ng/ml higher IGF‐1 = 1.03 [1.0–1.06], p = .015).ConclusionsHigher insulin‐like growth factor‐1 in cord blood is associated with asthma risk in the preschool years.

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“…However, a case-control study of 50 participants reported a positive association of serum IGF-1 with asthma. Nevertheless, the study was limited by a small sample size (21). Indeed, IGF-1 may play a crucial role in asthma, especially in airway hyperresponsiveness, airway inflammation, as well as smooth airway hyperplasia.…”

Section: Discussionmentioning

confidence: 99%

Circulating insulin-like growth factor-1 and risk of lung diseases: A Mendelian randomization analysis

Jiang

Shi

et al. 2023

Front. Endocrinol.

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BackgroundInsulin-like growth factor-1 (IGF-1) display a vital role in in the pathogenesis of lung diseases, however, the relationship between circulating IGF-1 and lung disease remains unclear.MethodsSingle nucleotide polymorphisms (SNPs) associated with the serum levels of IGF-1 and the outcomes data of lung diseases including asthma, chronic obstructive pulmonary disease (COPD), lung cancer and idiopathic pulmonary fibrosis (IPF) were screened from the public genome-wide association studies (GWAS). Two-sample Mendelian randomization (MR) analysis was then performed to assess the independent impact of IGF-1 exposure on these lung diseases.ResultsTotally, 416 SNPs related to circulating IGF-1 levels among 358,072 participants in UK Biobank. According to a primary casual effects model with MR analyses by the inverse variance weighted (IVW) method, the circulating IGF-1 was demonstrated a significantly related with the risk of asthma (OR, 0.992; 95% CI, 0.985-0.999, P=0.0324), while circulating IGF-1 showed no significant correlation with CODP (OR, 1.000; 95% CI, 0.999-1.001, P=0.758), lung cancer (OR, 0.979, 95% CI, 0.849-1.129, P=0.773), as well as IPIGFF (OR, 1.100, 95% CI, 0.794-1.525, P=0.568).ConclusionThe present study demonstrated that circulating IGF-1 may be causally related to lower risk of asthma.

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High serum levels of IGF-I and IGFBP3 may increase comorbidity risk for asthmatic patients

Cited by 8 publications

References 16 publications

IGF1R as a Potential Pharmacological Target in Allergic Asthma

IGF1R as a Potential Pharmacological Target in Allergic Asthma

Higher levels of insulin‐like growth factor‐1 in cord blood associate with risk of asthma at age 3

Circulating insulin-like growth factor-1 and risk of lung diseases: A Mendelian randomization analysis

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