title: Involvement of genes related to inflammation and cell cycle in idiopathic short stature.
abstract: Idiopathic Short Stature (ISS) defines a condition in which height is <-2SD compared to the mean of a reference population where systemic, endocrinological, nutritional or chromosomal disorders have not been identified and diagnosis is based on exclusion of any known causes of short stature. JAK/STAT pathway is triggered by GH binding to the GH receptor and promotes cellular growth through transcription of GH-responsive genes. In order to identify "candidate genes" differently expressed in ISS subjects with respect to control ones, we analyzed the expression of 84 genes related to JAK/STAT pathway by RT(2) Profiler PCR array approach in a total of 10 subjects. Then, we validated the observed data by Real Time PCR and ELISA assays in a major number of subjects. We found two genes that were differently expressed in ISS subjects with respect to the control group: CXCL9 and FCGR1A/CD64, both significantly up-regulated (fold change 2.17 and 1.70, respectively) and belonging to family of IFN-γ-inducible factors. Further, ISS subjects showed an increased gene expression of IFN-γ and IFI16, higher serum levels of IFN-γ but similar levels of CXCL9 when compared to healthy subjects. In addition, we showed a pubertal modulation of CXCL9 levels. These data suggest that inflammatory and regulatory factors of the cell cycle may be involved in the ISS condition, introducing a new perspective to its etiology.
authors.affiliation: Division of Pediatrics, Department of Medical Sciences, University of Piemonte Orientale, 28100, Novara, Italy. letizia.trovato@unito.it
authors.forename: Letizia
authors.initials: L
authors.lastname: Trovato
authors.forename: Flavia
authors.initials: F
authors.lastname: Prodam
authors.forename: Giulia
authors.initials: G
authors.lastname: Genoni
authors.forename: Francesca
authors.initials: F
authors.lastname: De Rienzo
authors.forename: Gillian E
authors.initials: GE
authors.lastname: Walker
authors.forename: Stefania
authors.initials: S
authors.lastname: Moia
authors.forename: Stefania
authors.initials: S
authors.lastname: Riccomagno
authors.forename: Simonetta
authors.initials: S
authors.lastname: Bellone
authors.forename: Gianni
authors.initials: G
authors.lastname: Bona
mesh_terms: D000293:Adolescent; D002453:Cell Cycle / Q000502:physiology; D054370:Chemokine CXCL9 / Q000378:metabolism; D018925:Chemokines / Q000378:metabolism; D002648:Child; D016207:Cytokines / Q000378:metabolism; D004393:Dwarfism, Pituitary / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D008297:Male; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D016133:Polymerase Chain Reaction; D017452:Receptors, IgG / Q000235:genetics / Q000378:metabolism
chemical_list: D054370:Chemokine CXCL9; D018925:Chemokines; D016207:Cytokines; C489017:FCGR1A protein, human; D009687:Nuclear Proteins; D010750:Phosphoproteins; D017452:Receptors, IgG; C076700:IFI16 protein, human