What is the difference between igf1 and igf2

Using Western blots, we demonstrated that IGF-2 supplementation increased the protein levels of pluripotency-associated marker OCT4 at days 3, 7, and 14 compared to PMSCs cultured in muscle differentiation media alone Figure 1 a , whereas other pluripotency-associated markers SOX2 Figure 1 b and Nanog Figure 1 c were decreased. In contrast, expression of muscle differentiation marker MHC was increased Figure 2 at 14 days after IGF-2 treatment compared to untreated controls, with fewer cells per field Supplementary Figure 1 suggesting that IGF-2 enhanced the terminal muscle differentiation process.

Concurrent with IGF-2 knockdown, we observed a decrease in pluripotency-associated marker OCT4 levels until day 3 with an increase at day 14 compared to scrambled siRNA control Figure 6 a. In contrast, SOX2 levels did not change Figure 6 b.

It is believed that if stem cells are to be used successfully in cell-based therapies for specific diseases, they must be initiated towards a progenitor cell of a desired lineage e. In addition, adequate cell numbers will be needed for effective therapy. Human placenta, which is usually discarded following birth, is a potential source of adult mesenchymal stem cells with functional capacity similar to bone marrow [ 31 — 34 ]. PMSCs also demonstrate low tumorigenicity with higher immunotolerance after transplantation, making them an ideal cell type for tissue regeneration therapies [ 35 , 36 ].

The IGF system is important for muscle development, growth, regeneration, and differentiation [ 10 , 11 , 13 , 37 , 38 ]. IGF-2 plays an important role during C2C12 differentiation and is considered the main myogenic factor in myoblast cells [ 39 ].

In this study, we showed that IGF-2 is synthesized and secreted into the extracellular space by PMSCs during muscle differentiation and the highest levels are expressed by fully differentiated muscle cells. Also, IGFBPs are expressed by many cell types, including skeletal muscle, and have been demonstrated to have functions that are dependent or independent of IGF binding [ 4 ].

IGFBPs are expressed by developing muscle cells and are important in myogenesis [ 40 , 41 ]. When L6E9 cells a myoblast cell line used to study late myogenesis are stimulated with IGF-1, these cells initiate a proliferative response. During this time of rapid cell division, the myogenic regulatory factors are inhibited. Approximately 30 hours later, there is a stimulation of myogenin expression [ 43 ]. We showed previously that IGF-2 secretion into the condition media was increased during and at the completion of muscle differentiation indicating that the synthesis of IGF-2 increased as the cells became more differentiated [ 26 ].

Increased OCT4 levels occurred alongside a decrease in SOX2 and Nanog levels which is expected in a mesodermal differentiation [ 45 ]; OCT4 is needed for differentiation as it supports downregulating pluripotency, and when deficient, cells are not able to differentiate [ 46 ].

IGF-1 and IGF-2 stimulate both proliferation and terminal differentiation of many tissues in developing embryos and adults. Previous studies in C2C12 cells show that as muscle differentiation progressed, IGF-2 stimulated its own expression and inhibited IGF-1 expression in a time- and dose-dependent manner [ 12 ]. Further investigation will be conducted to delineate these effects.

Moreover, IGFBP-6 expression has been previously associated with nonproliferative states and inhibition of IGF-2 dependent tumor cell growth in rhabdomyosarcoma, neuroblastoma, and colon cancer [ 48 ]. More specifically, neuroblastoma cells undergo a decrease in both cell proliferation and tumorigenic potency as a result of exogenous IGFBP-6 expression as IGFBP-6 sequesters IGF-2 preventing a mitogenic response in tumor cells [ 49 , 50 ].

Previous reports on the effects of IGFs on muscle differentiation used mouse cell lines [ 8 , 12 , 19 , 39 , 41 , 44 ], thus our study is one of the first to show the effects of IGF-dependent functions of IGFBP-6 on human MSC differentiation into skeletal muscle in vitro. The importance of IGFs in the human placenta is well defined in mediating growth and differentiation of the different cells of the chorionic villi [ 5 , 52 ]. IGF-2 also plays a role in the placenta at the early gestation, whereas IGF-1 is associated in later gestation [ 53 ].

Further investigation of the balance between IGFs and IGFBP-6 in PMSC myogenesis and delineating the receptors and signaling mechanisms governing muscle lineage development and regeneration will improve the success of cellular therapies in muscular dystrophies. The authors declare that there is no conflict of interest regarding the publication of this paper. Supplementary Materials. This is an open access article distributed under the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Article of the Year Award: Outstanding research contributions of , as selected by our Chief Editors. Read the winning articles. Journal overview. Special Issues. Doaa Aboalola 1,2,3,4 and Victor K. Academic Editor: Luca Vanella. Received 03 Aug Revised 28 Sep Accepted 10 Oct Published 14 Dec Abstract Insulin-like growth factors IGFs are critical components of the stem cell niche, as they regulate proliferation and differentiation of stem cells into different lineages, including skeletal muscle.

Introduction Insulin-like growth factor IGF system regulates cell growth, differentiation, migration, and cell survival through activation of several receptor-dependent signal transduction pathways [ 1 ].

Materials and Methods 2. Results 3. Figure 1. In contrast, IGF-2 treatment increased muscle differentiation marker levels at all time points. Figure 2. Immunocytochemistry was performed in triplicate with each antibody. Figure 3. Figure 4. Figure 5. The white arrows indicate muscle compaction. Figure 6. Figure 7. Figure 8. However, IGF-2 extracellular increase resulted in an increase in IGFBP-6 after commitment to the muscle lineage, resulting in full muscle lineage differentiation.

Figure 9. PMSC differentiation into skeletal muscle using the insulin-like growth factor system. FEBS Letters — Reviews in Aquatic Sciences 4 — Zoological Science 25 — Comparative Biochemistry and Physiology B 47 — Journal of Clinical Endocrinology and Metabolism 84 — Molecular and Cellular Endocrinology 57 — Domestic Animal Endocrinology 37 74 — Journal of Animal Science 83 — North American Journal of Aquaculture 70 — Journal of Endocrinology 81 — General and Comparative Endocrinology 31 — General and Comparative Endocrinology 75 — Comparative Biochemistry and Physiology B — American Journal of Physiology R — R International Review of Cytology 1 — Proceedings of the Society for Experimental Biology and Medicine — Hormone Research 71 36 — PNAS 92 — Molecular Marine Biology and Biotechnology 7 — PNAS 82 — Science — Journal of Fish Biology 70 — Endocrine Reviews 15 80 — Nutrition Reviews 57 — Molecular Endocrinology 4 — Biochimica et Biophysica Acta 63 — Gene 26 — Gene — Comparative Biochemistry and Physiology — International Review of Cytology — Sign in Create account.

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Free access. Download PDF. Check for updates. Get Permissions. Abstract Igf1 and Igf2 stimulate growth and development of vertebrates. Hepatocyte isolation and culture Fish were fasted for 1 day before hepatocyte isolation. Data analysis Gene expression data were log2 transformed before analysis. Figure 1 Effects of incubation time and GH treatment on A igf1 and B igf2 mRNA level in primary cultured tilapia hepatocytes and expressed relative to the time 0 control treatment rel.

Figure 4 Effects of insulin concentration on basal and GH-stimulated A igf1 and B igf2 mRNA level in primary cultured tilapia hepatocytes and expressed relative to the 0 insulin 0 GH control treatment rel. Figure 6 Effect of cortisol concentration on basal and GH-stimulated A igf1 and B igf2 mRNA level in primary cultured tilapia hepatocytes and expressed relative to the 0 cortisol 0 GH control treatment rel. Discussion This study shows that igf1 and igf2 mRNA levels are differentially regulated by insulin and cortisol in tilapia hepatocytes through direct effects and differential modulation of GH sensitivity.

Declaration of interest The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported. Breves JP Hirano T Grau EG Ionoregulatory and endocrine responses to disturbed salt and water balance in Mozambique tilapia exposed to confinement and handling stress.

Fruchtman S Jackson L Borski R Insulin-like growth factor I disparately regulates prolactin and growth hormone synthesis and secretion: studies using the teleost pituitary model. Griffen SC Russell SM Katz LS Nicoll CS Insulin exerts metabolic and growth-promoting effects by a direct action on the liver in vivo : clarification of the functional significance of the portal vascular link between the beta cells of the pancreatic islets and the liver. Houston B O'Neill IE Insulin and growth hormone act synergistically to stimulate insulin-like growth factor-I production by cultured chicken hepatocytes.

Moriyama S Yamaguchi K Takasawa T Chiba H Kawauchi H b Identification of two insulin-like growth factor IIs in the Japanese eel, Anguilla japonica : cloning, tissue distribution, and expression after growth hormone treatment and seawater acclimation. Plisetskaya EM Sullivan CV Pancreatic and thyroid hormones in rainbow trout Salmo gairdneri : what concentration does the liver see?

Ponce M Infante C Funes V Manchado M Molecular characterization and gene expression analysis of insulin-like growth factors I and II in the redbanded seabream, Pagrus auriga : transcriptional regulation by growth hormone. Reinecke M Collet C The phylogeny of the insulin-like growth factors. Rodgers BD Lau AO Nicoll CS Hypophysectomy or adrenalectomy of rats with insulin-dependent diabetes mellitus partially restores their responsiveness to growth hormone. Weber GM Grau EG Changes in serum concentrations and pituitary content of the two prolactins and growth hormone during the reproductive cycle in female tilapia, Oreochromis mossambicus , compared with changes during fasting.

Your current browser may not support copying via this button. Related Articles. CPP causes early onset of menarche and initial breast development in girls, psychosocial challenges, and early epiphyseal fusion in bones which reduces further growth spurts and thus may lower final height.

Treatment has the goal of preserving growth and height potential and can involve gonadotropin-releasing hormone GnRH analogs [ 2 ]. Treatment for CPP did not significantly affect the risk of cancer death, obesity, or metabolic disorders in to year-old women who had had CPP [ 3 ]. Poor nutrition may delay puberty while obesity promotes earlier initiation of puberty in girls [ 5 , 6 , 7 , 8 , 9 ].

The hormones, insulin, insulin-like growth factor-1 IGF-1 , and growth hormone GH are linked to precocious puberty [ 10 , 11 , 12 ]. GH and the IGF signaling pathways play major roles in regulating endocrine secretions involved in growth and sex maturation. Furthermore, puberty is delayed in female mice lacking IGF-1R, but not in males [ 14 ], suggesting a role of IGF-1 signaling in timing of puberty in females.

As tangential evidence, girls diagnosed with PP have a higher risk for developing breast cancer than girls without PP [ 17 ]. Abnormalities in the IGF signaling pathways affect progression of breast cancer [ 18 ]. The hypothesis of this study is that polymorphisms in one or more of the IGF genes may influence sex hormonal changes and affect the development of precocious puberty. The study included a total of girls with girls in the CPP group, and girls in the early puberty EP control group.

Follow-up visits occurred every 3 months. Eligibility criteria for the CPP group included continuing outpatient treatment at this hospital after outpatient examination and diagnosis with CPP. Exclusion criteria for the CPP group consisted of refusal to sign a consent form or having a disease that may have caused CPP, such as a chromosome anomaly; a noncancerous tumor in the brain or pituitary gland, brain injury; an infection in the brain e.

Exclusion criteria for the EP group were a GnRH homolog treatment, failure to continue to receive follow-ups, refusal of family members to sign the participation consent forms, or the aforementioned diseases or treatments in the exclusion criteria for CPP. Because all participating girls were 8 years old or younger, the parents or guardians of the participating girls uniformly provided signed informed consent.

Left-hand X-rays were performed on all subjects, and bone age BA was determined using the method of Greulich and Pyle [ 20 ]. Three replicate measurements of standing height were made using a wall-mounted stadiometer. BMI was calculated by dividing body weight kg by the square of height in meters m 2. Tanner stage standards were used to assess breast and pubic hair development [ 21 , 22 ].

After the subjects had fasted overnight, venous access was secured with a three-way stopcock and heparinized saline for the GnRH test. Serum E2 levels were measured using a commercial radioimmunoassay kit Diagnostic Systems Laboratories.

Sensitivity was 2. Sensitivity for both assays was 0. Intra- and inter-assay CVs were 4. The sensitivities were 0. The intra- and interassay CVs were 5. The sequences of primers used to amplify the related genotype and restriction enzyme for digestion as well as PCR products after digestion were listed in Table 1.

Strength of fluorescence for each sample was detected in each reaction cycle and plotted the fluorescent values against cycle number. The quantity and polymorphisms of each gene were observed by the intensity and color of fluorescence. Demographics and characteristics of CPP and control groups are summarized in Table 2.

The mean chronological age of all subjects was 8. There were significant differences between the CPP and control groups in most demographics and characteristics, except for GH levels Table 2. The serum IGF-1 level in the total population was positively correlated with most characteristics, especially bone age and LH. The correlations between IGF-1 levels and the different demographic and pathological features after adjusting for bone age are summarized in Table 5.

There were also no significant differences in genotype distribution of combinations of two SNPs in two distinct genes between the CPP and control groups Additional file 1 : Tables S2—1; S2—2.

We evaluated the association of demographic and pathological features with SNP genotype in both the control and CPP groups. Bone age v. IGF-1 v. We compared the association of demographic and pathological features with a combination of two genotypes in the control Fig.

However, none of the other demographic or pathological features were significantly associated with the combination of two SNP genotypes Additional file 1 : Table S4—2. Demographic and pathological features significantly associated with a combination of two SNP genotypes in the control group. Z score of weight v. Demographic and pathological features significantly associated with a combination of two SNP genotypes in the CPP group.

However, none of the other demographic or pathological features were significantly associated with the combination of three SNP genotypes Additional file 1 : Table S5—2.

Demographic and pathological features significantly associated with a combination of three SNP genotypes in the control group. Demographic and pathological features significantly associated with a combination of three SNP genotypes in the CPP group. Our findings showed that the IGF-1 serum levels of the CPP group exhibited a higher correlation with bone age, z-scores of height, z-scores of weight, and LH than those of the control group, regardless of adjustment for BMI.

Likewise, the distributions of the gene SNP combinations were similar. The IGF family plays an important role in stimulating skeletal growth, cell differentiation and metabolism, and has been shown to influence body composition [ 27 ].

IGF-2 has been reported to play a role in fetal development, while IGF-1 is expressed after birth [ 28 ]. This polymorphism was also shown to be associated with higher body weight, BMI, fat mass, and waist circumference in young subjects [ 27 ]. Homozygosity for the A variant was associated with the lowest mean IGF-1 concentration, whereas heterozygosity was associated with a slightly higher mean IGF-1 concentration. Homozygosity for the G variant was associated with the highest mean IGF-1 concentration.

AA homozygotes had a mean birth weight SDS of 0. However, the association between IGF-2 polymorphisms and size at birth remains controversial [ 30 ]. No polymorphisms of any IGF genes were associated with liver-related clinicopathological markers in serum [ 33 ]. It is structurally similar to insulin. Growth hormone stimulates the production of IGF1. Its production takes place throughout life, but it is optimal during pubertal growth.

IGF1 plays an important role in the metabolism of glucose together with insulin. Other than the metabolism of glucose, IGF1 is essential for normal growth and development, neuron survival, myelin sheath synthesis, astrocyte function, vessel growth, neuronal excitability and oligodendrogenesis.

IGF2 is the second peptide hormone that shares similarities with insulin. IGF-2 is the major growth promoting hormone during gestation. It also participates in the regulation of cell proliferation , growth, migration, differentiation and survival.