Growth impairment in IL-6-overexpressing transgenic mice is associated with induction of SOCS3 mRNA

• Published in: Growth hormone & IGF research 2003-02, Vol.13 (1), p.26-35
• Main Authors: Lieskovska, Jaroslava, Guo, Donglin, Derman, Eva
• Format: Article
• Language: English
• Subjects: Alpha-Globulins - metabolism; Animals; Blotting, Northern; Brain - growth & development; Brain - metabolism; Carrier Proteins - genetics; Carrier Proteins - metabolism; Cell Nucleus; DNA-Binding Proteins; Dwarfism; Electrophoretic Mobility Shift Assay; Female; Growth Disorders - metabolism; Growth hormone; Humans; IL-6; Immediate-Early Proteins - genetics; Immediate-Early Proteins - metabolism; Interleukin-6 - genetics; Interleukin-6 - metabolism; Intracellular Signaling Peptides and Proteins; Liver - growth & development; Liver - metabolism; Lung - growth & development; Lung - metabolism; Mice - growth & development; Mice, Transgenic; Muscle, Skeletal - growth & development; Muscle, Skeletal - metabolism; Proteins - genetics; Proteins - metabolism; Rats; Repressor Proteins; RNA, Messenger - biosynthesis; Signal Transduction; SOCS3; STAT3; STAT5; Suppressor of Cytokine Signaling 1 Protein; Suppressor of Cytokine Signaling 3 Protein; Suppressor of Cytokine Signaling Proteins; Trans-Activators; Transcription Factors; Transgenic mice
• ISSN: 1096-6374; 1532-2238
• DOI: 10.1016/S1096-6374(02)00135-1

MUP/hIL-6 transgenic mice overexpressing human interleukin-6 (IL-6) are growth-retarded. As documented here, the major transcriptional factor constitutively activated by IL-6 in the MUP/hIL6 transgenic mice was signal transducer and transactivator 3 (STAT3). Since STAT3 has been implicated in the expression of negative regulators of GH signaling, the suppressors of cytokine signaling (SOCS) genes, we have in this study examined the expression of SOCS1, SOCS2, SOCS3, and CIS genes.We found a large, 5-fold increase in SOCS3 mRNA in the liver, brain, skeletal muscle, and the lung of the MUP/hIL-6 transgenic mice. SOCS genes are thought to inhibit activation of transcriptional factor STAT5 by GH. Despite the induction of SOCS3 mRNA, STAT5 was activated in growth-retarded transgenic mice in response to elevated endogenous GH serum levels. The significance of activation of STAT3 and STAT5 transcription factors for cell proliferation and growth impairment in this mouse model is therefore discussed.