Selective receptor-mediated impairment of growth factor activity in neonatal- and X-linked adrenoleukodystrophy patients
-
Mazen Al-Essa
und
Gursev S. Dhaunsi
Abstract
Background
Neonatal adrenoleukodystrophy (n-ALD) and X-linked ALD (X-ALD) patients present with demyelination, poor growth and progressive mental retardation. Growth factors are known to play a vital role in the development of children.
Objective
To examine the mitogenic activity of various growth factors in skin fibroblasts from n-ALD and X-ALD patients.
Methods
Skin fibroblast cultures from n-ALD and X-ALD patients, and controls were treated with 50 ng/mL of platelet-derived growth factor (PDGF), basic fibroblast growth factor (bFGF) or insulin-like growth factor-1 (IGF-1) to examine DNA synthesis by 5-bromo-2′-deoxyuridine (BrdU) incorporation. Expression of receptors for PDGF, bFGF and IGF-1 was measured by western blotting. Serum levels of IGF-1 were assayed by enzyme-linked immunosorbent assay (ELISA).
Results
Fibroblasts from n-ALD and X-ALD patients had significantly (p < 0.01) less BrdU incorporation in response to fetal bovine serum (FBS). The mitogenic effect of PDGF, bFGF and IGF-1 was significantly lower in n-ALD as compared to control and X-ALD cells. X-ALD cells showed significant impairment in IGF-1-induced DNA synthesis. Expression of the FGF receptor (FGF-R) was significantly reduced in n-ALD cells. PDGF receptor remained unaffected, and IGF-1 receptor (IGF-1R) expression and serum IGF-1 levels were significantly (p < 0.01) reduced in n-ALD and X-ALD patients as compared to controls.
Conclusions
Growth factor activity differs in n-ALD and X-ALD patients, with marked impairment of IGF-1 function through receptor down-regulation.
Acknowledgments
The authors would like to thank Mrs. Nini Mathews and Mr. BS Srivastava for their technical assistance.
Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Research funding: None declared.
Employment or leadership: None declared.
Honorarium: None declared.
Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.
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©2019 Walter de Gruyter GmbH, Berlin/Boston
Artikel in diesem Heft
- Frontmatter
- Review
- Effect of safflower yellow on early type II diabetic nephropathy: a systematic review and meta-analysis of randomized controlled trials
- Original Articles
- Genomic study via chromosomal microarray analysis in a group of Romanian patients with obesity and developmental disability/intellectual disability
- Clinical and molecular characteristics and time of diagnosis of patients with classical galactosemia in an unscreened population in Turkey
- Assessment of retinal thickness as a marker of brain masculinization in children with congenital adrenal hyperplasia: a pilot study
- Auditory event-related potentials demonstrate early cognitive impairment in children with subclinical hypothyroidism
- Cardiovascular risk factors in children with type 1 diabetes mellitus
- The relationship between serum FGF-23 concentration and insulin resistance, prediabetes and dyslipidemia in obese children and adolescents
- The metabolic consequences of overweight in a cohort of children with type 1 diabetes
- The spectrum of pediatric adrenal insufficiency: insights from 34 years of experience
- Growth screening in children aged 3–5 years: a useful tool for public health programs in community pediatrics
- Selective receptor-mediated impairment of growth factor activity in neonatal- and X-linked adrenoleukodystrophy patients
- Determinants for low bone mineral density in pre-school children: a matched case-control study in Wuhan, China
- Genetic polymorphisms associated with obesity and non-alcoholic fatty liver disease in Asian Indian adolescents
- Maturity onset diabetes of the young (MODY) in Chinese children: genes and clinical phenotypes
- Severe, persistent neonatal hypoglycemia as a presenting feature in patients with congenital hypopituitarism: a review of our case series
- Case Reports
- Short stature in a boy with atypical progeria syndrome due to LMNA c.433G>A [p.(Glu145Lys)]: apparent growth hormone deficiency but poor response to growth hormone therapy
- A novel mutation leading to the lethal form of carnitine palmitoyltransferase type-2 deficiency
- Diagnosis of cyclic Cushing’s disease manifests as early morning hyperglycemia in a patient with previously well-controlled type 1 diabetes
- Short Communication
- Replacement of breastfeeding with medical food for the treatment of galactosemia and phenylketonuria: maternal stress
Artikel in diesem Heft
- Frontmatter
- Review
- Effect of safflower yellow on early type II diabetic nephropathy: a systematic review and meta-analysis of randomized controlled trials
- Original Articles
- Genomic study via chromosomal microarray analysis in a group of Romanian patients with obesity and developmental disability/intellectual disability
- Clinical and molecular characteristics and time of diagnosis of patients with classical galactosemia in an unscreened population in Turkey
- Assessment of retinal thickness as a marker of brain masculinization in children with congenital adrenal hyperplasia: a pilot study
- Auditory event-related potentials demonstrate early cognitive impairment in children with subclinical hypothyroidism
- Cardiovascular risk factors in children with type 1 diabetes mellitus
- The relationship between serum FGF-23 concentration and insulin resistance, prediabetes and dyslipidemia in obese children and adolescents
- The metabolic consequences of overweight in a cohort of children with type 1 diabetes
- The spectrum of pediatric adrenal insufficiency: insights from 34 years of experience
- Growth screening in children aged 3–5 years: a useful tool for public health programs in community pediatrics
- Selective receptor-mediated impairment of growth factor activity in neonatal- and X-linked adrenoleukodystrophy patients
- Determinants for low bone mineral density in pre-school children: a matched case-control study in Wuhan, China
- Genetic polymorphisms associated with obesity and non-alcoholic fatty liver disease in Asian Indian adolescents
- Maturity onset diabetes of the young (MODY) in Chinese children: genes and clinical phenotypes
- Severe, persistent neonatal hypoglycemia as a presenting feature in patients with congenital hypopituitarism: a review of our case series
- Case Reports
- Short stature in a boy with atypical progeria syndrome due to LMNA c.433G>A [p.(Glu145Lys)]: apparent growth hormone deficiency but poor response to growth hormone therapy
- A novel mutation leading to the lethal form of carnitine palmitoyltransferase type-2 deficiency
- Diagnosis of cyclic Cushing’s disease manifests as early morning hyperglycemia in a patient with previously well-controlled type 1 diabetes
- Short Communication
- Replacement of breastfeeding with medical food for the treatment of galactosemia and phenylketonuria: maternal stress
