Impact Of Insulin-like Growth Factor-1 Research Articles

The impact of IGF-1 on alveolar bone remodeling and BMP-2 expression in orthodontic tooth movement in diabetic rats.

Orthodontic tooth movement is linked to alveolar bone reconstruction. As a regulator of cell proliferation, insulin-like growth factor 1 (IGF-1) plays an important role in osteoporotic fracture healing. This study aims to investigate the effect of IGF-1 on alveolar bone remodeling in diabetic rats. Sprague Dawley (SD) rats were randomly divided into 3 groups, including a control group, a model group established with streptozotocin (STZ) injection to prepare the diabetic rats (type 1 diabetes), and an IGF-1 group of diabetic rats receiving daily intraperitoneal injections of 1.0 mg/kg IGF-1. Nickel-titanium coil springs were used to pull the first molar forward to establish the model. The maxillary first to third molars and the surrounding alveolar bone were collected to measure tooth movement distance. Hematoxylin and eosin (H&E) staining was applied to detect the pathological changes in the periodontal tissue. Real-time polymerase chain reaction (PCR) and western blot were adopted to measure bone morphogenetic protein 2 (BMP-2) mRNA and protein expression. Enzyme-linked immunosorbent assays (ELISAs) were used to measure interleukin-1α (IL-1α) levels in the serum. The tooth movement distance was significantly decreased, BMP-2 expression was downregulated, and IL-lα levels were enhanced in the model group compared to the control group (p < 0.05). However, the tooth movement distance was increased, BMP-2 expression was increased, and IL-lα levels were reduced in the IGF-1 group compared to the model group (p < 0.05). Hematoxylin and eosin staining showed that alveolar bone destruction was attenuated in the IGF-1 group, while the new bone was not active in the model group. Diabetes can damage alveolar bone remodeling in orthodontic tooth movement. The IGF-1 promotes alveolar bone remodeling by inhibiting inflammation and upregulating BMP-2 expression.

IGF-1 regulates the growth of fibroblasts and extracellular matrix deposition in pelvic organ prolapse.

This study was carried out to observe the impact of insulin-like growth factor-1 (IGF-1) on human vaginal fibroblasts (HVFs) in the context of pelvic organ prolapse (POP) and to explore its effects on mitogen-activated protein kinases (MAPK) and nuclear factor-κB (NF-κB) signaling pathways. First, it was found that IGF-1 expression reduced in the vaginal wall tissues derived from POP compared to that in non-POP cases. Then the role of IGF-1 was explored in HVFs and thiazolyl blue tetrazolium bromide (MTT) and flow cytometry were used to detect cell viability and cell apoptosis. Western blot assay and quantitative real-time polymerase chain reaction were used to detect the protein and mRNA expression. The results showed that knockdown of IGF-1 inhibited the cell viability of HVFs, promoted the cell apoptosis of HVFs, and decreased the expression of types I and III collagen in HVFs, which was through inhibiting the expression of IGF-1 receptor and MAPK/NF-κB pathways. However, IGF-1 plasmid had the opposite effects on HVFs. In conclusion, our results showed that IGF-1 could activate MAPK and NF-κB pathways, thereby enhancing collagen metabolism and the growth of vaginal wall fibroblasts then to inhibit POP development.

IGF-1R stimulation alters microglial polarization via TLR4/NF-κB pathway after cerebral hemorrhage in mice

Intracerebral hemorrhage (ICH) is a common neurological disease, causing severe disability and even deaths. Stem cell transplantation has been increasingly used in stroke therapy, and neural stem cells (NSCs) are a good source for stem cell transplantation. However, the regulatory mechanism of NSCs remains unclear. In this study, we examined the impact of insulin-like growth factor-1 (IGF-1) secreted by NSCs on microglial polarization following ICH in adult C57BL/6 mice. Mouse models of ICH were established by collagenase injection. ICH mice received NSC transplantation 1 h after model establishment. Firstly, the changes of microglial polarization in cerebral tissues of ICH mice were detected by immunofluorescence and ELISA. Secondly, the molecular mechanism underlying the microglial polarization was evaluated repeatedly with the application of IGF-1R siRNA and IGF-1R-mediated inhibition. We assessed the brain water content and behavioral deficits of ICH mice 12, 24, 48, and 72 h after surgery. The survival of neurons in the brain was examined using Nissl staining and TUNEL staining at 72 h. The TLR4/NF-κB pathway implicated in ICH-induced inflammation was profiled by Western blot analysis and immunohistochemistry. Finally, the changes in microglia after ICH in mice were re-examined under different doses of rhIGF-1. In summary, NSC transplantation changed microglial polarization in ICH mice. IGF-1R inhibition and knockdown reversed the therapeutic effect of NSCs, and rhIGF-1 had an anti-inflammatory effect. The results of this study suggest that IGF-1R stimulation is a potential target for stem cell-based treatment of cerebral hemorrhage and may attenuate inflammatory response in the brain after bleeding.

New insights into the protection of growth hormone in cisplatin-induced nephrotoxicity: The impact of IGF-1 on the Keap1-Nrf2/HO-1 signaling

Aims: Cisplatin (CDDP) is an effective antineoplastic agent, however, its serious nephrotoxicity limits therapeutic use. Human growth hormone (hGH) has proved antioxidant and anti-inflammatory activities. The present study aimed to investigate the nephroprotective effects of hGH against CDDP-induced nephrotoxicity and the mechanisms underlying this nephroprotection. Main Methods: Male albino rats injected with CDDP (7 mg/kg) and nephrotoxicity indices, oxidative stress and inflammatory biomarkers (high mobility group box protein-1 (HMGB-1), soluble epoxide hydrolase (sEH), and nuclear factor-kappa B (NF-κB)) were assessed. Also, insulin-like growth factor-1 (IGF-1) and Nuclear factor-erythroid-2 (Nrf2)/heme oxygenase-1 (HO-1) pathway were assessed. Key findings: hGH (1 mg/kg) improved kidney function and antioxidant systems and showed intact renal tubular epithelium. Cisplatin upregulated the HMGB-1/NF-κB and downregulated Nrf2/HO-1 pathways which were reversed by hGH and aligned with increased renal IGF-1 expression. Also, IGF-1/sEH crosstalk might be involved in hGH nephroprotection. Moreover, hGH downregulated HSP70 and caspase-3 expressions. Significance: these results concluded that hGH can attenuate the inflammation and oxidative stress attained by CDDP probably through inhibition of Nrf2/HO-1 pathway. We also suggested that Keap1/Nrf2-mediated upregulation of the antioxidant HO-1 might inhibit HMGB-1/NF-κB signaling and thus provide the principal protection mechanism offered by hGH against CDDP-induced kidney injury.

A predictive score for retinopathy of prematurity by using clinical risk factors and serum insulin-like growth factor-1 levels.

To detect the impact of insulin-like growth factor-1 (IGF-1) and other risk factors for the early prediction of retinopathy of prematurity (ROP) and to establish a scoring system for ROP prediction by using clinical criteria and serum IGF-1 levels. The study was conducted with 127 preterm infants. IGF-1 levels in the 1st day of life, 1st, 2nd, 3rd and 4th week of life was analyzed. The score was established after logistic regression analysis, considering the impact of each variable on the occurrences of any stage ROP. A validation cohort containing 107 preterm infants was included in the study and the predictive ability of ROP score was calculated. Birth weights (BW), gestational weeks (GW) and the prevalence of breast milk consumption were lower, respiratory distress syndrome (RDS), bronchopulmonary dysplasia (BPD) and necrotizing enterocolitis (NEC) were more frequent, the duration of mechanical ventilation and oxygen supplementation was longer in patients with ROP (P<0.05). Initial serum IGF-1 levels tended to be lower in newborns who developed ROP. Logistic regression analysis revealed that low BW (<1250 g), presence of intraventricular hemorrhage (IVH) and formula feeding increased the risk of ROP. Afterwards, the scoring system was validated on 107 infants. The negative predictive values of a score less than 4 were 84.3%, 74.7% and 79.8% while positive predictive values were 76.3%, 65.5% and 71.6% respectively. In addition to BW <1250 g and IVH, formula consumption was detected as a risk factor for the development of ROP. Breastfeeding is important for prevention of ROP in preterm infants.

Enhancing engineered vascular networks in vitro and in vivo: The effects of IGF1 on vascular development and durability

Creation of functional, durable vasculature remains an important goal within the field of regenerative medicine. Engineered biological vasculature has the potential to restore or improve human tissue function. We hypothesized that the pleotropic effects of insulin-like growth factor 1 (IGF1) would enhance the engineering of capillary-like vasculature. The impact of IGF1 upon vasculogenesis was examined in in vitro cultures for a period of up to 40days and as subcutaneous implants within immunodeficient mice. Co-cultures of human umbilical vein endothelial cells and human bone marrow-derived mesenchymal stem cells in collagen-fibronectin hydrogels were supplemented with either recombinant IGF1 protein or genetically engineered cells to provide sustained IGF1. Morphometric analysis was performed on the vascular networks that formed in four concentrations of IGF1. IGF1 supplementation significantly enhanced de novo vasculogenesis both in vitro and in vivo. Effects were long-term as they lasted the duration of the study period, and included network density, vessel length, and diameter. Bifurcation density was not affected. However, the highest concentrations of IGF1 tested were either ineffective or even deleterious. Sustained IGF1 delivery was required in vivo as the inclusion of recombinant IGF1 protein had minimal impact. IGF1 supplementation can be used to produce neovasculature with significantly enhanced network density and durability. Its use is a promising methodology for engineering de novo vasculature to support regeneration of functional tissue.

Adipose stem cells from chronic pancreatitis patients improve mouse and human islet survival and function

BackgroundChronic pancreatitis has surgical options including total pancreatectomy to control pain. To avoid surgical diabetes, the explanted pancreas can have islets harvested and transplanted. Immediately following total pancreatectomy with islet autotransplantation (TP-IAT), many islet cells die due to isolation and transplantation stresses. The percentage of patients remaining insulin free after TP-IAT is therefore low. We determined whether cotransplantation of adipose-derived mesenchymal stem cells (ASCs) from chronic pancreatitis patients (CP-ASCs) would protect islets after transplantation.MethodsIn a marginal mass islet transplantation model, islets from C57BL/6 mice were cotransplanted with CP-ASCs into syngeneic streptozotocin-treated diabetic mice. Treatment response was defined by the percentage of recipients reaching normoglycemia, and by the area under the curve for glucose and c-peptide in a glucose tolerance test. Macrophage infiltration, β-cell apoptosis, and islet graft vasculature were measured in transplanted islet grafts by immunohistochemistry. mRNA expression profiling of 84 apoptosis-related genes in islet grafts transplanted alone or with CP-ASCs was measured by the RT2 Profiler™ Apoptosis PCR Array. The impact of insulin-like growth factor-1 (IGF-1) on islet apoptosis was determined in islets stimulated with cytokines (IL-1β and IFN-γ) in the presence and absence of CP-ASC conditioned medium.ResultsCP-ASC-treated mice were more often normoglycemic compared to mice receiving islets alone. ASC cotransplantation reduced macrophage infiltration, β-cell death, suppressed expression of TNF-α and Bcl-2 modifying factor (BMF), and upregulated expressions of IGF-1 and TNF Receptor Superfamily Member 11b (TNFRSF11B) in islet grafts. Islets cultured in conditioned medium from CP-ASCs showed reduced cell death. This protective effect was diminished when IGF-1 was blocked in the conditioned medium by the anti-IGF-1 antibody.ConclusionCotransplantation of islets with ASCs from the adipose of chronic pancreatitis patients improved islet survival and islet function after transplantation. The effects are in part mediated by paracrine secretion of IGF-1, suppression of inflammation, and promotion of angiogenesis. ASCs from chronic pancreatitis patients have the potential to be used as a synergistic therapy to enhance the efficacy of islet transplantation following pancreatectomy.

IGF‐1 deficiency resists cardiac hypertrophy and myocardial contractile dysfunction: role of microRNA‐1 and microRNA‐133a

This study was designed to examine the impact of insulin-like growth factor-1 (IGF-1) deficiency on abdominal aortic constriction (AAC)-induced cardiac geometric and functional changes with a focus on microRNA-1, 133a and 208, which are specially expressed in hearts and govern cardiac hypertrophy and stress-dependent cardiac growth. Liver-specific IGF-1-deficient (LID) and C57/BL6 mice were subject to AAC. Echocardiographic and cardiomyocyte function were assessed 4 wks later. Haematoxylin and eosin staining was used to monitor myocardial morphology. Western blot and real-time PCR were used to detect protein and miR expression, respectively. Neonatal rat cardiomyocytes (NRCMs) were transfected with miRs prior to IGF-1 exposure to initiate cell proliferation. Immunohistochemistry and [3H] Leucine incorporation were used to detect cell surface area and protein abundance. C57 mice subject to AAC displayed increased ventricular wall thickness, decreased left ventricular end diastolic and end systolic dimensions and elevated cardiomyocyte shortening capacity, all of which were attenuated in LID mice. In addition, IGF-1 deficiency mitigated AAC-induced increase in atrial natriuretic factor, GATA binding protein 4, glucose transporter 4 (GLUT4) and Akt phosphorylation. In contrast, neither AAC treatment nor IGF-1 deficiency affected glycogen synthase kinase 3b, mammalian target of rapamycin, the Glut-4 translocation mediator Akt substrate of 160 kD (AS160) and protein phosphatase. Levels of miR-1 and -133a (but not miR-208) were significantly attenuated by AAC in C57 but not LID mice. Transfection of miR-1 and -133a obliterated IGF-1-induced hypertrophic responses in NRCMs. Our data suggest that IGF-1 deficiency retards AAC-induced cardiac hypertrophic and contractile changes via alleviating down-regulation of miR-1 and miR-133a in response to left ventricular pressure overload.

The impact of insulin-like growth factor-1, growth hormone, and oxidative stress in the experimental model of juvenile and adult hypothyroid retinal degeneration

Background: The pathophysiological mechanisms involved in hypothyroid retinal damage are still being debated. Materials and methods: Ninety-six pups of albino rats were equally divided into control, hypothyroid model and thyroid supplement groups. Each group was separated into juvenile and adult subgroups that were sacrificed at day 20 and 60 postnatally, respectively. Pups in the hypothyroid group were born to mothers who received 0.05 mg Carbimazole/day/pregnant female orally during gestation and at 20 days of lactation in juvenile subgroup. The adult subgroup received the hypothyroid agent until day 60 postnatally. The thyroid supplement group received antithyroid agent, then were treated with L-thyroxine orally (10 ug/kg body weight) for one month. Results: A significant reduction in body weight, temperature, heart rate, levels of Triiodothyronine (T3), Tetra-iodothyronine T4), growth hormone (GH) and Insulin-like growth factor (1GF-1), and antioxidant enzymes and an increase in systolic pressure and lipid peroxidation (LP) products were evident in hypothyroid subgroups associated with a decreasing thickness and degeneration of retina l layers. Thyroid supplementation group showed a partial normalization of the measured mediators accompanied by recovery of structural changes especially in the juvenile subgroup. Conclusions: Thyroid hormone has a vital role in normal retinal growth. GH, IGF-1 and oxidative stress are also significant mediators of retinal degeneration.

The impact of insulin-like growth factor-1 on the pattern of cardiac elongation factor-2 variants in a model of overload.

Because of its key role in proteosynthesis, the total content of elongation factor-2 (EF-2) and the distribution of six main EF-2 variants were investigated after Pseudomonas Exotoxin A catalyzed [37P]ADP-ribosylation using 1D-PAGE and isoelectric focusing (IEF) in a rat model of hemodynamic overload with variable degrees of cardiac hypertrophy: Chronic NO-synthase inhibition by L-NAME (N-omega-nitro-L-arginine-methyl-ester; 0.75 mg/ml drinking water) induced arterial hypertension without hypertrophy but myocardial apoptosis; additional treatment with IGF-1 (osmotic micropumps) did not modify hypertension but reduced apoptosis allowing moderate hypertrophy of the left ventricles. Total EF-2 did not significantly increase in rats with hemodynamic overload with or without IGF-1 supplementation. A positive correlation was found between an acidic EF-2 variant and apoptosis (p = 0.01). Hypertrophy under additional IGF-1 was combined with a shift of the EF-2 variants to basic subtypes (p < 0.01). This finding may be indicative of the trophic potency of IGF-1.