Human umbilical cord blood mesenchymal stem cells (hUCB-MSCs) are used in tissue repair and regeneration; however, the mechanisms involved are not well understood. We investigated the hair growth-promoting effects of hUCB-MSCs treatment to determine whether hUCB-MSCs enhance the promotion of hair growth. Furthermore, we attempted to identify the factors responsible for hair growth. The effects of hUCB-MSCs on hair growth were investigated in vivo, and hUCB-MSCs advanced anagen onset and hair follicle neogeneration. We found that hUCB-MSCs co-culture increased the viability and up-regulated hair induction-related proteins of human dermal papilla cells (hDPCs) in vitro. A growth factor antibody array revealed that secretory factors from hUCB-MSCs are related to hair growth. Insulin-like growth factor binding protein-1 (IGFBP-1) and vascular endothelial growth factor (VEGF) were increased in co-culture medium. Finally, we found that IGFBP-1, through the co-localization of an IGF-1 and IGFBP-1, had positive effects on cell viability; VEGF secretion; expression of alkaline phosphatase (ALP), CD133, and β-catenin; and formation of hDPCs 3D spheroids. Taken together, these data suggest that hUCB-MSCs promote hair growth via a paracrine mechanism.
Alkaline Phosphatase ; Alopecia ; Cell Survival ; Coculture Techniques ; Fetal Blood* ; Hair Follicle ; Hair* ; Humans* ; In Vitro Techniques ; Insulin-Like Growth Factor Binding Protein 1 ; Insulin-Like Growth Factor I ; Intercellular Signaling Peptides and Proteins* ; Mesenchymal Stromal Cells ; Regeneration ; Stem Cells* ; Umbilical Cord* ; Vascular Endothelial Growth Factor A

The length of IGF1R 3'UTR is greater than 7 kb. The structure of IGF1R 3'UTR is complex, with multiple binding sites of miRNAs. IGF1R is involved in the regulation of MAPK and PI3K/AKT signaling pathways and theformation and development of tumors. Bioinformatics analysis can reveal the structure features of IGF1R, which provides ideas for further research. The analysis shows that the binding sites between IGF1R and miRNAs have the highest mutation rate in Neuroblastoma. We analyzed the structure of 3'UTR, miRNAs binding sites, physical and chemical properties, hydrophilic-hydrophobic property, glycosylation and phosphorylation sites, secondary structure and tertiary structure modeling of IGF1R. The locations and names of amino acids interacting in IGF1R and IGF1 were obtained by molecular docking. Therefore, if IGF1R 3'UTR is mutated, the capacity of IGF1R combined with miRNAs will reduce and the IGF1R expression will be up-regulated, and the function of miRNAs will be repressed. We can change the sites of IGF1R to combine with IGF1 to repress the function of IGF1R and IGF1. Then the function of IGF1R will be repressed.
Binding Sites ; Computational Biology ; Humans ; Insulin-Like Growth Factor I ; MicroRNAs ; chemistry ; Molecular Docking Simulation ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Receptor, IGF Type 1 ; chemistry ; Signal Transduction

Increasing evidence suggests an important role of the insulin-like growth factor (IGF)-IGF binding protein (IGFBP) axis in the maintenance of normal glucose and lipid metabolism. Significant changes occur in the local IGF-I-IGFBPs environment in response to the diabetic milieu. A significant reduction of serum IGF-I levels was observed in patients with type 1 diabetes mellitus (T1DM). Inversely, considerably increased serum levels of IGF-I and IGFBP-3 levels were detected in individuals with glucose intolerance including T2DM. Recently, several prospective studies indicated that baseline levels of IGF-I and IGFBPs are associated with the development of diabetes. These findings suggest that disturbances in insulin and IGF-I-IGFBP axis can affect the development of glucose intolerance including diabetes.
Axis* ; Carrier Proteins ; Diabetes Mellitus* ; Diabetes Mellitus, Type 1 ; Glucose ; Glucose Intolerance ; Humans ; Insulin ; Insulin-Like Growth Factor Binding Protein 1 ; Insulin-Like Growth Factor Binding Protein 3 ; Insulin-Like Growth Factor Binding Proteins* ; Insulin-Like Growth Factor I ; Lipid Metabolism

Breast Neoplasms ; genetics ; metabolism ; Carcinoma, Squamous Cell ; genetics ; metabolism ; Colorectal Neoplasms ; genetics ; metabolism ; Endometrial Neoplasms ; genetics ; metabolism ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; Head and Neck Neoplasms ; genetics ; metabolism ; Humans ; Insulin-Like Growth Factor Binding Protein 1 ; genetics ; metabolism ; Insulin-Like Growth Factor Binding Protein 3 ; genetics ; metabolism ; Insulin-Like Growth Factor Binding Protein 5 ; genetics ; metabolism ; Insulin-Like Growth Factor Binding Proteins ; genetics ; metabolism ; Lung Neoplasms ; genetics ; metabolism ; Male ; Ovarian Neoplasms ; genetics ; metabolism ; Polymorphism, Genetic ; Promoter Regions, Genetic ; Prostatic Neoplasms ; genetics ; metabolism

PURPOSE: IGFBP-3 leads to the induction of insulin resistance in 3T3-L1 adipocytes. We carried out a series of experiments to elucidate the effects of IGFBP-3 on adipokines and gene expressions. METHODS: We treated fully-differentiated 3T3-L1 adipocytes with IGFBP-3 (0.5, 1, and 2 microg/mL) for one day and measured the mRNA levels of adiponectin, leptin, resistin, and TNF-alpha by RT-PCR, and adiponectin, leptin, resistin, and IL-6 protein levels in the culture supernatant were measured using multiplex adipokine assay ELISA Kits (Linco Research, St. Charles, Missouri). Gene expression in 3T3-L1 adipocyte cells using a microarray method was performed. RESULTS: IGFBP-3 inhibited the expression of adiponectin, leptin, resistin, and TNF-alpha mRNA. IGFBP-3 at 0.5 and 1 micro/mL decreased adiponectin release, but IL-6 release was increased at 2 micro/mL IGFBP-3. A dose-dependent inhibition of leptin was released by IGFBP-3 at 50%. Resistin release was decreased by 40%. The effect of IGFBP-3 on the gene expression in 3T3-L1 adipocyte cells using a microarray assay related to an increase of agouti-realted proteins (Agrp) and Janus kinase 2 (JAK2), and a decrease of the ras homolog gene family (Rhoq), acyl-CoA synthetase long-chain family member 6 (Acsl6), and the interleukin-1 receptor-associated kinase 1 (Irak1). CONCLUSION: IGFBP-3 regulates several adipokines gene expressions that are known to modulate insulin sensitivity, and this regulation may be attributable to the insulin resistance effect of IGFBP-3 on adipocytes.
Adipocytes ; Adipokines ; Adiponectin ; Enzyme-Linked Immunosorbent Assay ; Gene Expression ; Humans ; Insulin Resistance ; Insulin-Like Growth Factor Binding Protein 3 ; Interleukin-1 Receptor-Associated Kinases ; Interleukin-6 ; Janus Kinase 2 ; Leptin ; Ligases ; Proteins ; Resistin ; RNA, Messenger ; Tumor Necrosis Factor-alpha

OBJECTIVETo study the effects of astragaloside on the expression of insulin-like growth factor-1 (IGF-1) and associated proteins in mice with viral myocarditis.

METHODSSixty-five 4-week-old BALB/C mice were randomly divided into 5 groups: normal control, astragaloside control, untreated myocarditis, low-dose and high-dose astragaloside-treated myocarditis. The BALB/C mice in the later three groups were intraperitoneally injected with CVB3. The low-dose and high-dose astragaloside-treated myocarditis groups were given astragaloside of 0.07 and 0.6 mg/kg•d, respectively by intragastric administration. Fifteen days later, the samples of blood and muscular tissues were obtained. The expression of IGF-1 in plasma was measured using ELISA. The levels of IGF-1 and associated proteins in muscular tissues were measured by immunohistochemistry. The expression of IGF-1 mRNA in muscular tissues was examined by RT-polymerase chain reaction (RT-PCR).

RESULTSThe expression of IGF-1 and associated proteins increased significantly in mice infected with CVB3. High-dose astragaloside treatment reduced the expression of IGF-1 and associated proteins, but low-dose astragaloside did not.

CONCLUSIONSHigh-dose astragaloside may reduce the expression of IGF-1 and associated proteins in mice with acute viral myocarditis, possibly thus providing protective effects on muscular tissues.

Acute Disease ; Animals ; Coxsackievirus Infections ; drug therapy ; metabolism ; Drugs, Chinese Herbal ; therapeutic use ; Enterovirus B, Human ; Insulin-Like Growth Factor Binding Protein 3 ; analysis ; Insulin-Like Growth Factor I ; analysis ; genetics ; Male ; Mice ; Mice, Inbred BALB C ; Myocarditis ; drug therapy ; metabolism ; Myocardium ; chemistry ; RNA, Messenger ; analysis ; Receptor, IGF Type 1 ; analysis ; Saponins ; therapeutic use ; Triterpenes ; therapeutic use

Insulin-like growth factor (IGF) is closely associated with cardiovascular diseases. Low IGF-I level and high insulin-like growth factor binding protein-1 (IGFBP-1) level in serum can be used as a marker in predicting the long term morbidity and mortality of acute myocardial infarction (AMI). The article reviews the recent advances in IGFBP-1 in the prognosis of AMI.
Humans ; Insulin-Like Growth Factor Binding Protein 1 ; blood ; Insulin-Like Growth Factor I ; metabolism ; Myocardial Infarction ; blood ; Prognosis

BACKGROUND: Uterine leiomyomas are common benign smooth muscle tumors among the reproductive aged-women. The research has been aimed to identify the differentially expressed genes between normal myometrium and leiomyoma and to investigate the effects of E2 on their expression. METHODS: Gene microarray analysis was performed to identify the differentially expressed genes between normal myomerium and leiomyoma. The data was confirmed at protein level by tissue microarray. RESULTS: Gene microarray analysis revealed 792 upregulated genes in leiomyoma. Four genes (tropomyosin 4 [TPM4], collagen, type IV, alpha 2 [COL4alpha2], insulin-like growth factor binding protein 5 [IGFBP5], tripartite motif-containing 28 [TRIM28]) showed the most dramatic upregulation in all leiomyoma samples. Tissue microarray analyses of 262 sample pairs showed significantly elevated expression of TPM4, IGFBP5, estrogen receptor-alpha, and progesterone receptor (PR) protein in leiomyoma from the patients in their forties, COL4alpha2 in the forties and fifties age-groups, and TRIM28 in the thirties age-group. PR, insulin-like growth factor 1 (IGF-1), IGF-1 receptor (IGF-1R) and IGFBP5 were induced by E2 in in vitro culture of tissue explants from which cells migrated throughout the plate. Among these, PR, IGF-1, IGFBP5 genes showed higher expression in tissue compared to cells-derived from tissue in leiomyoma and IGF-1R in leiomyoma cell. CONCLUSIONS: This observation implies the importance of the whole tissue context including the cells-derived from tissue in the research for the understanding of molecular mechanism of leiomyoma. Here, we report higher expression of TRIM28 in leiomyoma for the first time and identify E2-responsive genes that may have important roles in leiomyoma development.
Animals ; Collagen Type IV ; Estrogens ; Female ; Gene Expression ; Humans ; Immunohistochemistry ; Insulin-Like Growth Factor Binding Protein 5 ; Insulin-Like Growth Factor I ; Leiomyoma ; Mice ; Microarray Analysis ; Myometrium ; Oligonucleotide Array Sequence Analysis ; Receptor, IGF Type 1 ; Receptors, Progesterone ; Smooth Muscle Tumor ; Tissue Array Analysis ; Transcriptome ; Up-Regulation ; Uterus

OBJECTIVE: Intrauterine growth is influenced by multiple factors like genetic, nutritional, environmental and hormonal factors. As birth weight is reported to be related to perinatal morbidity and mortality, we aimed to compare umbilical cord blood adiponectin, IGF-I, IGFBP-1, insulin and leptin levels between small for gestational age (SGA) and appropriate for gestational age (AGA) neonates at birth to investigate the influence of these factors on birth weight and ponderal index. METHODS: We investigated retrospectively 30 pregnant women with SGA and 30 pregnant women with AGA who delivered at Ewha Womans University Hospital and their babies from January 2007 to December 2007. Fetal umbilical cord venous blood adiponectin, IGF-I, IGFBP-1, insulin and leptin levels from SGA and AGA neonates were obtained at the time of delivery. The definition used to identify cases of SGA was individual birth weight ratio of less than 10th percentile and the definition of ponderal index (PI) was [BW (g)/ (height (cm))3]x100. RESULTS: Umbilical cord blood adiponectin, IGF-I and IGF/IGFBP ratio were significantly lower (P<0.05) in SGA than AGA. And umbilical cord blood IGFBP-1 were significantly higher (P<0.05) in SGA than AGA. But there was no significant difference in umbilical cord blood insulin and leptin levels between SGA and AGA neonates. Positive correlation was noted between adiponectin and IGF-I, IGF/IGFBP ratio, insulin and leptin. Negative correlation was noted between adiponectin and IGFBP-1, IGF-I and IGFBP-1. On multiple regression analysis, adiponectin and IGF-I were significant factors associated with body weight (BW), but only IGFBP-1 was significant factor associated with PI. CONCLUSION: These results suggest that fetal adiponectin, IGF-I, IGFBP-1 may have an important role in regulation of intrauterine growth and we will expect that evaluation of adiponectin and IGF-I in SGA may be helpful in prediction of neonatal outcome, and IGFBP-1 may be useful in diagnosis of asymmetric intrauterine growth retardation (IUGR).
Adiponectin ; Birth Weight ; Body Weight ; Female ; Fetal Blood ; Fetal Growth Retardation ; Gestational Age ; Humans ; Infant, Newborn ; Insulin ; Insulin-Like Growth Factor Binding Protein 1 ; Insulin-Like Growth Factor I ; Leptin ; Parturition ; Pregnant Women ; Retrospective Studies ; Umbilical Cord

AIMUnderstanding the response of mesenchymal stem cells (MSCs) to mechanical strain and their consequent gene expression patterns will broaden our knowledge of the mechanobiology of distraction osteogenesis.

METHODOLOGYIn this study, a single period of cyclic mechanical stretch (0.5 Hz, 2,000 microepsilon) was performed on rat bone marrow MSCs. Cellular proliferation and alkaline phosphatase (ALP) activity was examined. The mRNA expression of six bone-related genes (Ets-1, bFGF, IGF-II, TGF-beta, Cbfa1 and ALP) was detected using real-time quantitative RT-PCR.

RESULTSThe results showed that mechanical strain can promote MSCs proliferation, increase ALP activity, and up-regulate the expression of these genes. A significant increase in Ets-1 expression was detected immediately after mechanical stimulation, but Cbfa1 expression became elevated later. The temporal expression pattern of ALP coincided perfectly with Cbfa1.

CONCLUSIONThe results of this study suggest that mechanical strain may act as a stimulator to induce differentiation of MSCs into osteoblasts, and that these bone-related genes may play different roles in the response of MSCs to mechanical stimulation.

Alkaline Phosphatase ; analysis ; Animals ; Antigens, Surface ; analysis ; Biomechanical Phenomena ; Bone Marrow Cells ; physiology ; Cell Culture Techniques ; Cell Differentiation ; physiology ; Cell Proliferation ; Core Binding Factor Alpha 1 Subunit ; analysis ; Fibroblast Growth Factor 2 ; analysis ; Insulin-Like Growth Factor II ; analysis ; Mesenchymal Stromal Cells ; physiology ; Osteoblasts ; physiology ; Osteogenesis, Distraction ; Pluripotent Stem Cells ; physiology ; Proto-Oncogene Protein c-ets-1 ; analysis ; Rats ; Stress, Mechanical ; Transforming Growth Factor beta ; analysis ; Up-Regulation ; physiology