Linked Life Data

20080849

Source:http://linkedlifedata.com/resource/pubmed/id/20080849

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2010-3-5
pubmed:abstractText
Context: NF-kappaB is a family of transcription factors involved in cell proliferation, differentiation, and apoptosis. Objective: We have recently demonstrated that NF-kappaB is expressed in the growth plate and it mediates the growth-promoting effects of IGF-I on chondrogenesis and longitudinal bone growth. Humans with defects of the NF-kappaB pathway exhibit growth failure, which suggests a possible regulatory role for NF-kappaB in statural growth. We have previously reported a child with ectodermal dysplasia, immunodeficiency, and growth retardation, harboring a heterozygous mutation of IkappaBalpha, an essential component of the NF-kappaB pathway. Since he was found with low IGF-l and IGFBP-3, and elevated GH secretion, an IGF-l generation test was carried out: baseline IGF-l was low and only responded to a high dose of GH. Thus, the diagnosis of GH resistance was made. Results: To assess the underlying mechanisms of his GH resistance, we cultured the patient's skin fibroblasts with GH and/or IGF-I. While both GH and IGF-l induced cell proliferation and NF-kappaB activity in controls' fibroblasts, they had no effect on the patient's fibroblasts. In the fibroblasts of the patient's father (who displays mosaicism for the IkappaBalpha mutation), GH and IGF-l elicited an attenuated stimulatory effect. In addition, GH stimulated STAT5 phosphorylation and IGF-l mRNA expression in controls ' and the father's fibroblasts, while IGF-l induced PI3K activity and mRNA and protein expression of TDAG51, a target gene for IGF-I. In contrast, none of these effects was elicited by GH or IGF-l in the patient's fibroblasts. Conclusion: Our findings suggest that this patient's IkappaBalpha mutation caused GH and IGF-l resistance which, in turn, contributed to his growth failure.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1945-7197
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
95
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1220-8
pubmed:meshHeading
pubmed-meshheading:20080849-Analysis of Variance, pubmed-meshheading:20080849-Blotting, Western, pubmed-meshheading:20080849-Cell Proliferation, pubmed-meshheading:20080849-Cells, Cultured, pubmed-meshheading:20080849-Fibroblasts, pubmed-meshheading:20080849-Growth Disorders, pubmed-meshheading:20080849-Human Growth Hormone, pubmed-meshheading:20080849-Humans, pubmed-meshheading:20080849-I-kappa B Proteins, pubmed-meshheading:20080849-Insulin-Like Growth Factor Binding Protein 3, pubmed-meshheading:20080849-Insulin-Like Growth Factor I, pubmed-meshheading:20080849-Male, pubmed-meshheading:20080849-Mutation, pubmed-meshheading:20080849-Phosphorylation, pubmed-meshheading:20080849-RNA, Messenger, pubmed-meshheading:20080849-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:20080849-STAT5 Transcription Factor, pubmed-meshheading:20080849-Signal Transduction, pubmed-meshheading:20080849-Skin, pubmed-meshheading:20080849-Transcription Factors
pubmed:year
2010
pubmed:articleTitle
Growth hormone and insulin-like growth factor I insensitivity of fibroblasts isolated from a patient with an I{kappa}B{alpha} mutation.
pubmed:affiliation
St. Christopher's Hospital for Children, 3601 A Street, Philadelphia, Pennsylvania 19134, USA.
pubmed:publicationType
Journal Article, Case Reports