Involvement of genes related to inflammation and cell cycle in Idiopathic Short Stature
- 278 Downloads
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 RT2 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.
KeywordsCytokines Chemokines Gene profile Idiopathic short stature Cellular cycle
Conflict of interest
The authors declare that they have no conflict of interest.
- 1.Cohen P, Rogol AD, Deal CL, Saenger P, Reiter EO, Ross JL, Chernausek SD, Savage MO, Wit JM (2008) ISS Consensus Workshop participants: consensus statement on the diagnosis and treatment of children with idiopathic short stature: a summary of the Growth Hormone Research Society, the Lawson Wilkins Pediatric Endocrine Society, and the European Society for Paediatric Endocrinology Workshop. J Clin Endocrinol Metab 93(11):4210–4217PubMedCrossRefGoogle Scholar
- 3.Rojas-Gil AP, Ziros PG, Diaz L, Kletsas D, Basdra EK, Alexandrides TK, Zadik Z, Frank SJ, Papathanassopoulou V, Beratis NG, Papavassiliou AG, Spiliotis BE (2006) Growth hormone/JAK-STAT axis signal-transduction defect. A novel treatable cause of growth failure. FEBS J 273(15):3454–3466PubMedCrossRefGoogle Scholar
- 11.Ambrosio R, Fimiani G, Monfregola J, Sanzari E, De Felice N, Salerno MC, Pignata C, D’Urso M, Ursini MV (2002) The structure of human STAT5A and B genes reveals two regions of nearly identical sequence and an alternative tissue specific STAT5B promoter. Gene 285(1–2):311–318PubMedCrossRefGoogle Scholar
- 14.SMILA Neonatal Standards for North-East Italy, Montecatini, September 1996, pp 26–31Google Scholar
- 15.Arikawa E, Sun Y, Wang J, Zhou Q, Ning B, Dial SL, Guo L, Yang L (2008) Cross-platform comparison of SYBR Green real-time PCR with TaqMan PCR, microarrays and other gene expression measurement technologies evaluated in the MicroArray Quality Control (MAQC) study. BMC Genomics 9:328PubMedCrossRefGoogle Scholar
- 16.Trovato L, Riccomagno S, Prodam F, Genoni G, Walker GE, Moia S, Bellone S, Bona G (2011) Isolated GHD: investigation and implication of JAK/STAT related genes before and after rhGH treatment. Pituitary. doi: 10.1007/s11102-011-0354-8
- 23.Tillinger W, Jilch R, Jilma B, Brunner H, Koeller U, Lichtenberger C, Waldhör T, Reinisch W (2009) Expression of the high-affinity IgG receptor FcRI (CD64) in patients with inflammatory bowel disease: a new biomarker for gastroenterologic diagnostics. Am J Gastroenterol 104:102–109PubMedCrossRefGoogle Scholar