Differential capacity of the parthenogenetic embryonic stem cells (PESCs) is still under controversy and the mechanisms of its neural induction are yet poorly understood. Here we demonstrated neural lineage induction of PESCs by addition of insulin-like growth factor-2 (Igf2), which is an important factor for embryo organ development and a paternally expressed imprinting gene. Murine PESCs were aggregated to embryoid bodies (EBs) by suspension culture under the leukemia inhibitory factor-free condition for 4 days. To test the effect of exogenous Igf2, 30 ng/ml of Igf2 was supplemented to EBs induction medium. Then neural induction was carried out with serum-free medium containing insulin, transferrin, selenium, and fibronectin complex (ITSFn) for 12 days. Normal murine embryonic stem cells derived from fertilized embryos (ESCs) were used as the control group. Neural potential of differentiated PESCs and ESCs were analyzed by immunofluorescent labeling and real-time PCR assay (Nestin, neural progenitor marker; Tuj1, neuronal cell marker; GFAP, glial cell marker). The differentiated cells from both ESC and PESC showed heterogeneous population of Nestin, Tuj1, and GFAP positive cells. In terms of the level of gene expression, PESC showed 4 times higher level of GFAP expression than ESCs. After exposure to Igf2, the expression level of GFAP decreased both in derivatives of PESCs and ESCs. Interestingly, the expression level of $Tuj1$ increased only in ESCs, not in PESCs. The results show that IGF2 is a positive effector for suppressing over-expressed glial differentiation during neural induction of PESCs and for promoting neuronal differentiation of ESCs, while exogenous Igf2 could not accelerate the neuronal differentiation of PESCs. Although exogenous Igf2 promotes neuronal differentiation of normal ESCs, expression of endogenous $Igf2$ may be critical for initiating neuronal differentiation of pluripotent stem cells. The findings may contribute to understanding of the relationship between imprinting mechanism and neural differentiation and its application to neural tissue repair in the future.
Moon, Jin Wook;Chang, Yoon Soo;Han, Chang Hoon;Kang, Shin Myung;Park, Moo Suk;Byun, Min Kwang;Chung, Wou Young;Park, Jae Jun;Yoo, Kyeong Nam;Shin, Ju Hye;Kim, Young Sam;Chang, Joon;Kim, Sung Kyu;Kim, Hee Jung;Kim, Se Kyu
Tuberculosis and Respiratory Diseases
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v.58
no.4
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pp.359-366
/
2005
Background : IGFBP-3 inhibits the mitogenic and anti-apoptotic activity of IGF by blocking the binding of IGF to its receptor. However, under certain circumstances, IGFBP-3 can enhance the activity of IGF by protecting IGF from its degradation. More than half of the interindividual variations in IGFBP-3 levels are known to be genetically determined by the polymorphism at -202 locus of IGFBP-3 gene. Method : We attempted to ascertain whether A-202C polymorphic variation of IGFBP-3 gene constitutes a risk factor for non-small cell lung cancer (NSCLC), using PCR-restriction fragment length polymorphism (RFLP). Our study included 104 NSCLC patients and 104 age-, gender-, and smoking status-matched control subjects. Result : In the 104 NSCLC subjects, the genotypic frequencies at the -202 site were as follows: AA = 67 (64.4%), AC = 35 (33.7%), and CC = 2 (1.9%). We did detect significant differences in the genotypic distribution between the NSCLC and the control subjects (p<0.05), and the NSCLC risk correlated significantly with AA genotype at the -202 locus (AA>AC>CC). Using CC genotype as a reference, the odds ratio (OR) for the subjects with AC genotype was 2.60 (95% CI: 0.89 - 8.60), and the OR associated with AA genotype was 5.89 (95% CI: 1.92 - 21.16). Conclusion : These results indicate that the dysregulation of IGF axis should now be considered as another important risk factor for NSCLC, and a potential target for novel antineoplastic therapies and/or preventative strategies in high-risk groups.
Four 4-month old Charolais${\times}$Dorset male sheep (initial liveweight $25.0{\pm}1.1\;kg$), fitted with rumen and abomasal fistulas and nourished by total intragastric infusions, were used to study the relationships between methionine (Met) supply, nitrogen (N) retention and plasma insulin-like growth factor-I (IGF-I). Four graded levels of Met, i.e. 0 g/16 g N, 1.76 g/16 g N, 3.52 g/16 g N and 7.04 g/16 g N, were infused into abomasums as experimental treatments. The sheep and treatments were allocated in a $4{\times}3$ incomplete Latin square design (Yudon square design). The experiment lasted 3 periods and each period was 10 days. Quadratic correlations were found between Met level (x, g/16 g N) and N retention (y, g/d): y = $-0.03x^2$+0.41x+2.62, $r^2$ = 0.66, n = 12, p = 0.008, and between methionine level (x, g/16 g N) and plasma IGF-I concentration (y, ng/ml): y = $0.80x^2$-4.53x+190.24, $r^2$ = 0.51, n = 12, p = 0.009. No significant correlation was found between plasma IGF-I (x, ng/ml) and N retention (y, g/d) (p>0.05). It was concluded that Met level had a significant influence on N retention and plasma IGF-I concentration whereas IGF-I might not be an important mediator in the regulation of N metabolism by Met in growing sheep nourished by total intragastric infusions.
Injection of bovine growth hormone (bGH) to lactating dairy cows increases milk yield and yields of milk components including fat. It is generally believed that most of the anabolic effects derived from bGH in animal tissues are primarily mediated by IGF-1. IGF-1 is a strong anabolic peptide in the plasma of animals and exerts mitogenic and metabolic effects on target cells. Contrary to most protein hormones, the majority of IGF-1 in circulation is bound to the binding proteins (IGFBPs) which are known to be responsible for modifying the biological actions of IGF-1, thus making determinations of IGF-1 actions more difficult. On the other hand, fat is a major milk component and the greatest energy source in milk. Currently, the fat content of milk is one of the major criteria used in determining milk prices. It has been known that flavor and texture of dairy products are mainly affected by milk fat and its composition. Acetyl-CoA carboxylase (ACC) is the rate limiting enzyme which catalyzes the conversion of acetyl-CoA to malonyl-CoA for fatty acid synthesis in 1ipogenic tissues of animals including bovine lactating mammary glands. In addition to the short-tenn hormonal regulation of ACC by changes in the catalytic efficiency per enzyme molecule brought about by phosphorylation and dephosphorylation of the enzyme, the long-term hormonal regulation of ACC by changes in the number of enzyme molecules plays an essential role in control of ACC and lipogenesis. Insulin, at supraphysiological concentrations, binds to IGF-1 receptors, thereby mimicking the biological effects of IGF-1. The receptors for insulin and IGF-1 share structural and functional homology. Furthermore, epidermal growth factor increased ACC activity in rat hepatocytes and adipocytes. Therefore, it can be assumed that IGF-1 mediating bGH action may increase milk fat production by stimulation ACC with phosphorylation (short term) and/or increasing amounts of the enzyme proteins (long term). Consequently, the main purpose of this paper is to give the readers not only the galactopoietic effects of bGH, but also the insight of bGH action with regard to stimulating milk fat synthesis from the whole body to the molecular levels.
Szalai, Klaudia;Tempfli, Karoly;Zsedely, Eszter;Lakatos, Erika;Gaspardy, Andras;Papp, Agnes Bali
Animal Bioscience
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v.34
no.4
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pp.662-669
/
2021
Objective: Effects of linseed oil (LO) supplementation on the fat content and fatty acid profile of breast meat, and the expression of three genes in the liver, breast muscle and fat tissues of commercial 154-day-old hybrid male turkeys were investigated. Methods: The animals in the control group were fed a commercially available feed and received no LO supplementation (n = 70), whereas animals in the LO group (n = 70) were fed the same basic diet supplemented with LO (day 15 to 21, 0.5%; day 22 to 112, 1%). The effect of dietary LO supplementation on fatty acid composition of breast muscle was examined by gas chromatography, and the expression of fatty acid desaturase 2 (FADS2), peroxisome proliferator activated receptor gamma (PPARγ), and insulin-like growth factor 1 (IGF1) genes was analysed by means of quantitative reverse transcription polymerase chain reaction. Results: The LO supplementation affected the fatty acid composition of breast muscle. Hepatic FADS2 levels were considerably lower (p<0.001), while adipose tissue expression was higher (p<0.05) in the control compared to the LO group. The PPARγ expression was lower (p<0.05), whereas IGF1 was higher (p<0.05) in the fat of control animals. There were no significant (p>0.05) differences in FADS2, PPARγ, and IGF1 gene expressions of breast muscle; however, omega-6/omega-3 ratio of breast muscle substantially decreased (p<0.001) in the LO group compared to control. Conclusion: Fatty acid composition of breast meat was positively influenced by LO supplementation without deterioration of fattening parameters. Remarkably, increased FADS2 expression in the liver of LO supplemented animals was associated with a significantly decreased omega-6/omega-3 ratio, providing a potentially healthier meat product for human consumption. Increased PPARγ expression in fat tissue of the LO group was not associated with fat content of muscle, whereas a decreased IGF1 expression in fat tissue was associated with a trend of decreasing fat content in muscle of the experimental LO group.
Objectives : In Korean medicine, a prescription of Sinsun-yukza-hwan (Shenxian-liuzi-wan, SSY) has been used in clinic for treatment of alopecia via oral. This study was performed to determine transdermal effects of the ethanol extract from SSY on hair growth and -related gene expressions in mice. Methods : We analyzed index compound, 5-hydroxy-methyl-2-furaldehyde (HMF), in SSY extract by ultra performance liquid chromatography (UPLC). 6 weeks old C57BL/6 mice with removed hair were used as an alopecia animal model. Mice were divided into 3 experimental groups including normal (3 water: 1 ethanol: 2 polyethylene glycol mixture as a vehicle), SSY extract and 5% minoxidil (as a positive control), treated groups. SSY was applied topically on the hair-shaved skin of C57BL/6 mice every day for 15 days. The color, thickness and density of hair were monitored every $5^{th}$ day by naked eye, photograph and phototrichogram using folliscope. Also hair growth-associated gene expressions were measured by immunoblotting assay. Results : Hair density of minoxidil or SSY-treated group was significantly increased compared to that of vehicle application on the $15^{th}$ day, respectively. And hair thickness of minoxidil and SSY groups was increased compared to that of vehicle treated group on the $15^{th}$ day, respectively. Induction of insulin-like-growth factor 1(IGF-1) and vascular endothelial growth factor (VEGF) were also significantly accelerated by SSY extract compared to those of vehicle-applied group. Conclusions : These results provide scientific evidence to support the potent multi-application of SSY as a cosmeceutical material for promoting hair growth.
A sodium-independent facilitative glucose transporter 1 (Glut1) is a major route by which glucose can be transported across the plasma membrane of mouse embryo. Although it has been known that insulin-like growth factor-I (IGF-I) promotes glucose transport into the mouse embryo, whether IGF-I directly regulates transcription of Glut1 has been uncovered in mouse preimplantation embryo. This study was aimed to elucidate the role of glucose and IGF-I in development and Glut1 expression in preimplantation mouse embryo. Two-cell embryos developed in blastocyst regardless of the glucose in the presence of pyruvate. IGF-I significantly increased the number of blastomeres in the mid-blastula. Deprivation of glucose did not affect the amount of Glut1 transcripts in morula cultured from 2-cell embryo. IGF-I potentiated Glut1 expression in morula cultured from 2-cell embryo even in the absence of glucose. Taken together, it is concluded that depletion of glucose does not promote Glut1 expression the in morula cultured form 2-cell embryo, and that increment of Glut1 expression possibly mediates embryotropic effect of IGF-I on preimplantation mouse embryo.
This study investigated the effect of snail extract on the growth parameters of old female rats (27 weeks). Rats were administered orally with snail extract at a dose of 100 mg/kg, 200 mg/kg, chondroitin sulfate 10 mg/kg and 0.9% saline (control) for 8 weeks. Bone mineral density (BMD) and serum concentrations of insulin-like growth factor 1 (IGF-1) and insulinlike growth factor-binding protein 3 (IGFBP-3) were significantly higher in rats exposed to snail extract for 8 weeks. MG-63 cells (human osteoblast-like cells) were treated with snail extract for 48 h. Their differentiation and proliferation was investigated with Western blot and morphological changes observed via immunofluorescence staining of ${\beta}-catenin$. Treatment with snail extract significantly increased the levels of growth factors including ${\beta}-catenin$ and IGF-1. The snail extract affected osteoblast formation. Morphological changes in MG-63 cells were observed via immunofluorescence staining. Treatment with snail extract increased the expression of ${\beta}-catenin$ in MG-63 cells. Results suggest that the treatment of MG-63 cells with snail extract increased the longitudinal growth and growth factor levels. Snail extract may be pharmacologically effective in osteogenic differentiation in vitro and represents a potential therapeutic agent for bone formation.
Patients with chronic renal failure, many of which treated with hemodialysis, present a high prevalence of impaired muscle strength which suggest that muscle mass parameters may be used as markers for changes in muscle in these patients. Measurement of handgrip strength (HGS) is a common, simple, and quick measure of muscle function an indicator of overall muscle strength which has been associated with physical activity and several anthropometric traits. Intercellular adhesion molecule-1 (ICAM-1) and insulin-like growth factor-1 (IGF-1) are biochemical markers associated with inflammatory processes which are a common consequence of dialysis. Additionally, hemodialysis patients frequently present signs of malnutrition and depression. This cross-sectional study aimed to evaluate if muscle and biochemical markers could be used to predict the risk of depression in hemodialysis patients. Several anthropometric parameters, nutrient intake, depression state and the serum levels of ICAM-1 and IGF-1 were determined and Pearson's correlation coefficient and/or Spearman's correlation coefficient were used to test the correlation between them. Our results do not show a correlation between HGF, IGF-1 and ICAM-1 with the depression status of the patients, but mid-arm muscle circumference (MAMC) was statistically and positively correlated with depression. Additionally, ICAM-1 levels were negatively correlated with HGS, MAMC, and IGF-1. Overall, the results of the present study suggest that HGS may be used as an indicator of cardiovascular diseases and MAMC may be a good predictor of the level of depression in hemodialysis patients, although further studies are required.
The majority of early embryonic mortality in pregnancy occurs during the peri-implantation stage, suggesting that this period is important for conceptus viability and the establishment of pregnancy. Successful establishment of pregnancy in all mammalian species depends on the orchestrated molecular events that transpire at the conceptus-uterine interface during the peri-implantation period. This maternal-conceptus interaction is especially crucial in pigs because in them non-invasive epitheliochorial placentation occurs, in which the pre-implantation phase is prolonged. During the pre-implantation period, conceptus survival and the establishment of pregnancy are known to depend on the developing conceptus receiving an adequate supply of histotroph, which contains a wide range of nutrients and growth factors. Evidence links growth factors including epidermal growth factor (EGF), insulin-like growth factor-I (IGF-I), vascular endothelial growth factor (VEGF), and colony-stimulating factor 2 (CSF2) to embryogenesis or implantation in various mammalian species; however, in the case of pig, little is known about such functions of these growth factors, especially their regulatory mechanisms at the maternal-conceptus interface. Our research group has presented evidence for promising growth factors affecting cellular activities of primary porcine trophectoderm (pTr) cells, and we have identified potential intracellular signaling pathways responsible for the activities induced by these factors. Therefore, this review focuses on promising growth factors at the maternal-conceptus interface regulating the development of the porcine conceptus and playing pivotal roles in implantation events during early pregnancy in pigs.
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