title: Growth impairment in IL-6-overexpressing transgenic mice is associated with induction of SOCS3 mRNA.
abstract: 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.
authors.affiliation: Department of Developmental and Structural Biology, Public Health Research Institute, 225 Warren Street, Newark, NJ 07103, USA.
authors.forename: Jaroslava
authors.initials: J
authors.lastname: Lieskovska
authors.forename: Donglin
authors.initials: D
authors.lastname: Guo
authors.forename: Eva
authors.initials: E
authors.lastname: Derman
mesh_terms: D000510:Alpha-Globulins / Q000378:metabolism; D000818:Animals; D015152:Blotting, Northern; D001921:Brain / Q000254:growth & development / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002467:Cell Nucleus; D004268:DNA-Binding Proteins; D024202:Electrophoretic Mobility Shift Assay; D005260:Female; D006130:Growth Disorders / Q000378:metabolism*; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins; D008099:Liver / Q000254:growth & development / Q000378:metabolism*; D008168:Lung / Q000254:growth & development / Q000378:metabolism*; D051379:Mice / Q000254:growth & development*; D008822:Mice, Transgenic; D018482:Muscle, Skeletal / Q000254:growth & development / Q000378:metabolism*; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D012097:Repressor Proteins; D015398:Signal Transduction; D000071222:Suppressor of Cytokine Signaling 1 Protein; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D015534:Trans-Activators; D014157:Transcription Factors
chemical_list: D000510:Alpha-Globulins; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D017874:Immediate-Early Proteins; D015850:Interleukin-6; D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins; D012333:RNA, Messenger; D012097:Repressor Proteins; D000071222:Suppressor of Cytokine Signaling 1 Protein; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D015534:Trans-Activators; D014157:Transcription Factors; C108944:SOCS1 protein, human; C106643:SOCS2 protein, human; C106644:SOCS3 protein, human; C491590:Socs1 protein, mouse; C491589:Socs1 protein, rat; C491409:Socs2 protein, mouse; C491408:Socs2 protein, rat; C491411:Socs3 protein, mouse; C491410:Socs3 protein, rat; C035737:major urinary proteins