Structural, gene expression, and functional analysis of the fugu (Takifugu rubripes) insulin-like growth factor binding protein-4 gene

2009 ◽  
Vol 296 (3) ◽  
pp. R558-R566 ◽  
Author(s):  
Mingyu Li ◽  
Yun Li ◽  
Ling Lu ◽  
Xianlei Wang ◽  
Qingli Gong ◽  
...  
Keyword(s):  
Growth Factor ◽  
Expression Patterns ◽  
Biological Action ◽  
Takifugu Rubripes ◽  
Insulin Like Growth Factor ◽  
Igf Binding Proteins ◽  
Physiological Regulation ◽  
Functional Conservation ◽  
Igf Receptors ◽  
And Function

The insulin-like growth factor (IGF) signaling pathway is a conserved pathway that regulates animal development, growth, metabolism, reproduction, and aging. The biological actions of IGFs are modulated by IGF-binding proteins (IGFBPs). Although the structure and function of fish IGFBP-1, -2, -3, and -5 have been elucidated, there is currently no report on the full-length structure of a fish IGFBP-4 nor its biological action. In this study, we cloned and characterized the IGFBP-4 gene from fugu. Sequence comparison, phylogenetic, and synteny analyses indicate that its chromosomal location, gene, and protein structure are similar to its mammalian orthologs. Fugu IGFBP-4 mRNA was easily detectable in all adult tissues examined with the exception of spleen. Older animals tended to have higher levels of IGFBP-4 mRNA in the muscle and eyes compared with younger animals. Starvation resulted in significant increases in IGFBP-4 mRNA abundance in the muscle, liver, gallbladder, and brain. Overexpression of fugu and human IGFBP-4 in zebrafish embryos caused a significant decrease in body size and somite number, suggesting that fugu IGFBP-4 inhibits growth and development, possibly by binding to IGFs and inhibiting their binding to the IGF receptors. These results provide new information about the structural and functional conservation, expression patterns, and physiological regulation of the IGFBP-4 gene in a teleost fish.

Effects of Maternal Diabetes on Fetal Expression of Insulin-Like Growth Factor and Insulin-Like Growth Factor Binding Protein MRNAs in the Rat

1995 ◽  
Vol 147 (2) ◽  
pp. R5-R8 ◽  
Author(s):  
Randal D. Streck ◽  
Veeraramani S. Rajaratnam ◽  
Renata B. Fishman ◽  
Peggy J. Webb
Keyword(s):  
Growth Factor ◽  
Mrna Expression ◽  
Fetal Growth ◽  
Fetal Liver ◽  
Expression Patterns ◽  
Maternal Diabetes ◽  
Limb Bud ◽  
Insulin Like Growth Factor ◽  
Igf Binding Proteins ◽  
Increased Risk

ABSTRACT Matemal diabetes is associated in humans and rats with an increased risk for fetal growth abnormalities and malformations. Therefore, the effect of maternal diabetes on expression of genes that regulate fetal growth and differentiation is of considerable interest. Developmental growth is regulated in part by the expression and availability of insulin-like growth factors (IGFs). Postnatal expression of a subset of the IGFs and IGF binding proteins (IGFBPs) has been demonstrated to be regulated in response to diabetes and other metabolic conditions. We used in situ hybridization to analyze the effect of maternal diabetes, induced by streptozotocin (STZ) prior to mating, upon prenatal rat IGF and IGFBP mRNA expression. At gestational day (GD) 14, the most striking effect of maternal diabetes on fetal IGF/IGFBP gene expression was a marked increase in the abundance of IGFBP-1 mRNA within the liver primordia of fetuses isolated from diabetic dams compared to age-matched controls. This upregulation cannot be entirely due to the approximately one-half-day delay in fetal development (based on limb bud staging) associated with maternal diabetes, as there was no gross difference in the level of IGFBP-1 mRNA between GD13 and GD14 control fetal livers. In contrast, the fetal mRNA expression patterns of IGF-I, IGF-II and IGFBP-2, -3, -4, -5 and -6 were not grossly altered by maternal diabetes. These data are consistent with the hypothesis that IGFBP-1 produced within the fetal liver and secreted into fetal circulation may play a role in regulating rat fetal growth.

scholarly journals Insulin-Like Growth Factor Pathway and the Thyroid

2021 ◽  
Vol 12 ◽  
Author(s):  
Terry J. Smith
Keyword(s):  
Growth Factor ◽  
Biological Effects ◽  
Normal Function ◽  
Insulin Like Growth Factor ◽  
Functional Protein ◽  
Igf Binding Proteins ◽  
Hormone Synthesis ◽  
Surface Receptors ◽  
Igf I ◽  
And Function

The insulin-like growth factor (IGF) pathway comprises two activating ligands (IGF-I and IGF-II), two cell-surface receptors (IGF-IR and IGF-IIR), six IGF binding proteins (IGFBP) and nine IGFBP related proteins. IGF-I and the IGF-IR share substantial structural and functional similarities to those of insulin and its receptor. IGF-I plays important regulatory roles in the development, growth, and function of many human tissues. Its pathway intersects with those mediating the actions of many cytokines, growth factors and hormones. Among these, IGFs impact the thyroid and the hormones that it generates. Further, thyroid hormones and thyrotropin (TSH) can influence the biological effects of growth hormone and IGF-I on target tissues. The consequences of this two-way interplay can be far-reaching on many metabolic and immunologic processes. Specifically, IGF-I supports normal function, volume and hormone synthesis of the thyroid gland. Some of these effects are mediated through enhancement of sensitivity to the actions of TSH while others may be independent of pituitary function. IGF-I also participates in pathological conditions of the thyroid, including benign enlargement and tumorigenesis, such as those occurring in acromegaly. With regard to Graves’ disease (GD) and the periocular process frequently associated with it, namely thyroid-associated ophthalmopathy (TAO), IGF-IR has been found overexpressed in orbital connective tissues, T and B cells in GD and TAO. Autoantibodies of the IgG class are generated in patients with GD that bind to IGF-IR and initiate the signaling from the TSHR/IGF-IR physical and functional protein complex. Further, inhibition of IGF-IR with monoclonal antibody inhibitors can attenuate signaling from either TSHR or IGF-IR. Based on those findings, the development of teprotumumab, a β-arrestin biased agonist as a therapeutic has resulted in the first medication approved by the US FDA for the treatment of TAO. Teprotumumab is now in wide clinical use in North America.

scholarly journals Insulin-like Growth Factor 1 Signaling in Mammalian Hearing

Genes ◽  
2021 ◽  
Vol 12 (10) ◽  
pp. 1553
Author(s):  
Ángela García-Mato ◽  
Blanca Cervantes ◽  
Silvia Murillo-Cuesta ◽  
Lourdes Rodríguez-de la Rosa ◽  
Isabel Varela-Nieto
Keyword(s):  
Hearing Loss ◽  
Growth Factor ◽  
Biological Effects ◽  
Expression Patterns ◽  
Peptide Hormone ◽  
Tyrosine Kinase Receptor ◽  
Insulin Like Growth Factor ◽  
Mammalian Development ◽  
Igf Binding Proteins ◽  
Igf System

Insulin-like growth factor 1 (IGF-1) is a peptide hormone belonging to the insulin family of proteins. Almost all of the biological effects of IGF-1 are mediated through binding to its high-affinity tyrosine kinase receptor, (IGF1R), a transmembrane receptor belonging to the insulin receptor family. Factors, receptors and IGF-binding proteins form the IGF system, which has multiple roles in mammalian development, adult tissue homeostasis, and aging. Consequently, mutations in genes of the IGF system, including downstream intracellular targets, underlie multiple common pathologies and are associated with multiple rare human diseases. Here we review the contribution of the IGF system to our understanding of the molecular and genetic basis of human hearing loss by describing, (i) the expression patterns of the IGF system in the mammalian inner ear; (ii) downstream signaling of IGF-1 in the hearing organ; (iii) mouse mutations in the IGF system, including upstream regulators and downstream targets of IGF-1 that inform cochlear pathophysiology; and (iv) human mutations in these genes causing hearing loss.

scholarly journals Insulin-like growth factor axis during embryonic development

Reproduction ◽  
2001 ◽  
pp. 31-39 ◽  
Author(s):  
GJ Allan ◽  
DJ Flint ◽  
K Patel
Keyword(s):  
Growth Factor ◽  
Expression Patterns ◽  
Limb Bud ◽  
Type I ◽  
Insulin Like Growth Factor ◽  
Igf Binding Proteins ◽  
Igf System ◽  
Type I Igf Receptor ◽  
Igf Binding ◽  
Mrna And Protein Expression

The insulin-like growth factor (IGF) axis has been studied extensively in the developing vertebrate embryo. Knockout experiments have demonstrated that both IGF-I and -II are required for normal development in the mouse embryo, and mRNA and protein expression patterns for both growth factors, together with those for the type I IGF receptor and the six IGF-binding proteins, have been analysed in embryos from different species. Although the unique temporal and spatial expression patterns of these genes indicates important roles for the IGF axis during organ and whole animal development, the variation and complexity of expression makes these roles difficult to unravel. However, one possible mechanism unifying the IGF system in development is programmed cell death (apoptosis), which has been shown to be important in sculpting embryonic tissues, and, in particular, the developing limb bud. In addition, the very early onset of expression of various IGF family members in chicken embryos further emphasizes the fundamental importance of this system in development. This article reviews the work that has been carried out in this area in the context of current understanding of the IGF system.

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