35 THERAPEUTIC EFFECTS OF INSULIN-LIKE GROWTH FACTOR-1 ON STRESS URINARY INCONTINENCE IN RATS WITH SIMULATED CHILD BIRTH TRAUMA INJURY
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You have accessJournal of UrologyUrodynamics/Incontinence/Female Urology: Basic Research I1 Apr 201235 THERAPEUTIC EFFECTS OF INSULIN-LIKE GROWTH FACTOR-1 ON STRESS URINARY INCONTINENCE IN RATS WITH SIMULATED CHILD BIRTH TRAUMA INJURY Yasuhiro Sumino, Satoru Yoshikawa, Hiromitsu Mimata, and Naoki Yoshimura Yasuhiro SuminoYasuhiro Sumino Pittsburgh, PA More articles by this author , Satoru YoshikawaSatoru Yoshikawa Pittsburgh, PA More articles by this author , Hiromitsu MimataHiromitsu Mimata Oita, Japan More articles by this author , and Naoki YoshimuraNaoki Yoshimura Pittsburgh, PA More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.078AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Insulin-like growth factor-1 (IGF-1) plays an important role in cell proliferation, survival and regeneration in various tissues. However, the therapeutic potential of IGF-1 for stress urinary incontinence (SUI) has not been explored. We examined the effect of IGF-1 in a rat model of SUI induced by stimulated birth trauma. METHODS Simulated birth trauma was induced by vaginal distension (VD) with an inflated balloon catheter for 4 hrs in the vagina of female SD rats. At 4, 7, 14 and 28 days after VD, (1) functional assessments were performed by measuring leak point pressure (LPP), urethral baseline pressure (UBP) and urethral responses during passive increment in intravesicular pressure and (2) the expression of IGF-1 and IGF-1 receptor (IGF1R) mRNA and protein in damaged tissues was examined by real-time RT-PCR and immunohistochemistry. Thereafter, human recombinant IGF-1 (hrIGF-1) (50 and 150μg/kg/day) or vehicle (saline) was continuously delivered from 1 day before VD using subcutaneous osmotic pumps. At 4 and 7 days after VD, the effect of IGF-1 treatment was examined by ELISA measurement of serum hrIGF-1, functional analyses (LPP, UBP and urethral response), and Western blotting analysis of Akt signal transduction pathways in urethral tissues. RESULTS After 4 and 7 days, VD rats had significantly reduced LPP, UBP and urethral responses, with a recovery to the normal level 14 and 28 days after VD. mRNA and protein levels of IGF-1 and IGF1R were significantly increased in the urethra and pudendal nerves 4 and 7 days after VD. IGF-1 treatment (50 and 150μg/kg/day) increased serum hrIGF-1 levels to 17.8±5.3 and 40.4±12.5 ng/ml, respectively. These IGF-1-treated groups showed significant improvement in LPP, UBP and urethral responses 4 and 7 days after VD (Figure). Moreover, phosphorylated Akt was highly expressed in the IGF-1-treated urethra. CONCLUSIONS IGF-1 treatment accelerates recovery from SUI induced by stimulated child birth trauma in rats, possibly through activation of the Akt signal transduction pathway, suggesting that IGF-1 has an important role in the recovery from childbirth-related SUI. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e14-e15 Peer Review Report Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Yasuhiro Sumino Pittsburgh, PA More articles by this author Satoru Yoshikawa Pittsburgh, PA More articles by this author Hiromitsu Mimata Oita, Japan More articles by this author Naoki Yoshimura Pittsburgh, PA More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...Altered expression of Insulin-like Growth Factor-1 (IGF-1), its receptor (IGF-1R), Connective Tissue Growth Factor (CTGF) and Hypoxia Inducible Factor-1 (HIF-1), has been implicated in tumorigenesis. So far, these factors have not been studied systematically in Pulmonary Carcinoids (PCs).To examine IGF-1, IGF-1R, CTGF and HIF-1 expression in PCs, and assess their prognostic value over established factors.Retrospective study of 121 PCs (104 Typical and 17 Atypical). The expression of growth factors was studied immunohistochemically and tumors were considered positive if immunoreactivity appeared in >50% of cells.All studied parameters were expressed in the majority of tumors (IGF-1, IGF-1R, CTGF and HIF-1, in 78.5%, 67%, 72% and 78%, respectively). Their expression tended to be more frequent in TCs and in tumors with Ki-67≤2% (significant only for HIF-1; 82 vs. 53%; p=0.023 and 83 vs. 63%; p=0.025 respectively). CTGF was the only factor correlated with more extensive disease (larger size; presence of lymph node and distant metastases). According to logistic regression analysis, only advanced age, Ki-67≥3.4% and lymph node involvement could predict the development of distant metastases.IGF-1, IGF-1R, CTGF and HIF-1 are avidly expressed in PCs; however, their presence did not appear to be of statistically significant value over established prognostic factors.
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Research progress of the correlation between porcine Insulin-like growth factor 1 (IGF-I) and growth
Abstract Insulin-like growth factor 1 ( IGF-I ) is an important factor which plays the roles in regulating animal growth, development and metabolism. IGF-I also called somatomedin C (SM - C) mainly mediate growth hormone that plays the roles of promoting growth and is a kind of polypeptide regulating cell proliferation and differentiation. The paper review influences of IGFBPS, SNPs of porcine IGF-I gene, IGF-I signaling pathway and feed level on IGF-I , moreover, the correlation between porcine insulin-like growth factor IGF-I and growth..
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The combination of insulin-like growth factor-I and platelet-derived growth factor-BB has previously been shown to stimulate healing of soft tissue wounds and the formation of bone and ligament around teeth. The purpose of the present study was to evaluate the effects of platelet-derived growth factor-BB and insulin-like growth factor-I individually and in combination on the healing of osseous wounds. Four standardized cortical wounds were created in each tibia of 11 adult Yucatan miniature pigs. The wounds in one tibia per animal were treated with either purified recombinant human insulin-like growth factor-I, platelet-derived growth factor-BB, or both in a methylcellulose gel. The wounds in each contralateral tibia received placebo gel alone. Coded serial sections of each wound were evaluated by computer-aided histomorphometry 21 days after surgery. The area and perimeter of the newly formed mineralized callus, the thickness of the total callus, and the percentage of mineralized tissue within the callus were significantly increased compared with the values of matched controls only in wounds treated with a combination of insulin-like growth factor-I and platelet-derived growth factor-BB. No significant differences in the measured parameters of callus formation were found in wounds treated with either insulin-like growth factor-I or platelet-derived growth factor-BB alone. Cartilage was present only in sites treated with insulin-like growth factor-I alone. These results suggest that the combination of platelet-derived growth factor-BB and insulin-like growth factor-I stimulates bone formation in wounds in long bones of adult animals and that these growth factors act via different pathways during the repair process.
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음경의 발기는 혈관계, 신경계, 내분비계와 음경해면체 평 활근이 복합적으로 작용하여 일어나는 현상이다 (1). 음경 해면체 평활근은 음경발기에 중요한 역할을 하는데 음경해 면체 평활근 세포의 분화와 증식에는 여러 성장인자가 관 여하는 것으로 알려져 있으며 최근 주목을 받고 있는 성장 인자는 Vascular endothelial growth factor (VEGF), Insulin like growth factor-1 (IGF-1), Growth hormone (GH), Platelet derived growth factor (PDGF), Transforming growth factor (TGF) 등이 다 (2-6). 이러한 성장인자들 중 IGF-1은 세포내에서 세포의 성장 과 분화에 영향을 미치며 세포막에 있는 IGF-1 수용체에 의 해 기능이 유도되는 것으로 알려져 있다 (7,8). 대부분의 순 환하는 IGF-1은 간에서 만들어지며 GH이 IGF-1의 합성과 분비의 조절에 관여한다 (9,10). IGF-1은 당뇨쥐에서 혈관 평활근 세포의 증식을 촉진하는 것으로 알려져 있는데, 정 상쥐의 대동맥에서도 in vivo 실험에서 고농도의 IGF-1을 투여했을 때 혈관 평활근 세포의 증식을 자극하는 것으로 보고되고 있다 (11). Lynch (12)는 치주조직에서 IGF-1과 PDGF를 함께 투여했을 때 섬유아세포의 이동과 성장이 크 게 촉진되었고 다른 어떤 단일 성장인자보다 골기질의 형 IGF-1이 인간의 음경해면체 평활근 세포의 성장에 미치는 영향
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Abstract The present study was undertaken to investigate the effect of insulin‐like growth factor‐1 on proteoglycan synthesis and the autocrine/paracrine mechanisms involving insulin‐like growth factor‐1 in the bovine coccygeal intervertebral disc. Insulin‐like growth factor‐1 stimulated proteoglycan synthesis in cultured cells of the nucleus pulposus of bovine intervertebral discs in a dose‐dependent manner, and the effect was inhibited by an anti‐insulin‐like growth factor‐1 monoclonal antibody. In situ hybridization histochemistry revealed the expression of insulin‐like growth factor‐1 mRNA in the cultured cells, and its production in these cells was demonstrated by radioimmunoassay. Insulin‐like growth factor‐1 receptor in the cultured cells was also demonstrated immunohistochemically. Scatchard analysis using an [ 125 I]insulin‐like growth factor‐1 binding assay showed that the cells cultured in monolayer had a single type of insulin‐like growth factor‐1 receptor, whose affinity and number were estimated to be 7.38 × 10 8 / M and 9.27 × 10 4 /cell, respectively. These results suggest that insulin‐like growth factor‐1 stimulates proteoglycan synthesis in cells of the nucleus pulposus and that these cells in culture have an insulin‐like growth factor‐1 autocrine/paracrine mechanism. The expressions of insulin‐like growth factor‐1 mRNA and insulin‐like growth factor‐1 receptor in disc tissue were greater in cells of the nucleus pulposus of fetal bovine intervertebral discs than in those of the adult discs. These findings suggest that the action of autocrine/paracrine insulin‐like growth factor‐1 is more active in cells of the young nucleus pulposus than in cells of mature subjects.
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Study Design. Age-related fluctuations in insulin-like growth factor-I dependent proteoglycan synthesis in rat intervertebral disc cells were investigated. Objectives. The purpose of this study was to determine whether synthetic responses to insulin-like growth factor-I decline with age and to explore the possibility that an age-related increase in the expression of insulin-like growth factor binding proteins suppresses matrix synthesis in intervertebral disc cells. Summary and Background Data. Several studies have reported that the responsiveness of chondrocytes to insulin-like growth factor-I decreases with age and furthermore that this phenomenon may be related to increased expression of insulin-like growth factor binding proteins by chondrocytes. Materials and Methods. Nucleus pulposus tissue and cells were obtained from the coccygeal vertebrae of 8-week-old, 40-week-old, and 120-week-old rats. Age-related changes in the expression of insulin-like growth factor-I and its receptor were assessed together with insulin-like growth factor-I dependent proteoglycan synthesis by the cultured nucleus pulposus cells. Also, western blot analysis of insulin-like growth factor binding protein-1 was carried out, and further examination was performed of insulin-like growth factor-I signal transduction through tyrosine phosphorylation of insulin receptor substrate-1, which is a signal transducer of insulin-like growth factor-I. Results. Semiquantitative reverse transcription polymerase chain reaction analysis indicated that the expression of insulin-like growth factor-I receptor in 120-week cells decreased clearly in comparison with the cells of younger animals. By contrast, insulin-like growth factor-I dependent proteoglycan synthesis decreased with age, and the sharpest decline of synthesis was found between 8-week and 40-week cells, although the level of insulin-like growth factor-I/insulin-like growth factor-I receptor gene expression was maintained in 40-week-old animals. Consistent with the results of proteoglycan synthesis, the expression of phosphorylated insulin receptor substrate-1 decreased with age. Thus, the expression of insulin-like growth factor binding protein-1 and proteoglycan synthesis was investigated by use of Long R3 insulin-like growth factor-I, which was not influenced by insulin-like growth factor binding proteins. Insulin-like growthfactor binding protein-1 was strongly expressed in 40-week cells in comparison withthe expression in 8-week cells. Furthermore, proteoglycan synthesis in 40-week cells supplemented with Long R3 insulin-like growth factor-I was upregulated in comparison with that in 40-week cells supplemented with insulin-like growth factor-I. Conclusion. The present findings indicate that the age-related decline in insulin-like growth factor-I dependent proteoglycan synthesis in nucleus pulposus is caused, at least in part, by the increase in insulin-like growth factor binding proteins at the early stages of aging, and further suggest that a loss of proteoglycan synthesis during the late stages of aging is caused by the downregulation of insulin-like growth factor-I receptor in addition to an increase in insulin-like growth factor binding proteins.
Intervertebral Disc
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Platelet‐derived growth factor (PDGF) and insulin‐like growth factor I (IGF‐I) in combination have previously been shown to enhance periodontal regeneration. The objective of this study was to further characterize the biological effects of this combination of growth factors in non‐human primates and compare the effects to those of each growth factor individually. Ligature‐induced periodontitis was initiated in 10 cynomolgus monkeys. After periodontal lesions were established, surgery was performed, and either a methylcellulose gel vehicle or vehicle containing 10 μg each of either PDGF‐BB, IGF‐I or both PDGF‐BB and IGF‐I was applied to exposed root surfaces. Biopsies were taken 4 and 12 wk after treatment and the extent of periodontal regeneration was assessed by histomorphometry. At both 4 and 12 wk vehicle‐treated lesions generally revealed minimal osseous defect fill (ODF) (8.5±2.1% and 14.5±5.7%, respectively) and new attachment (NA) (34.1±5.2% and 26.6±10.5%, respectively). IGF‐I treatment did not significantly alter healing compared to vehicle in any parameter at both 4 and 12 wk. PDGFBB‐treated sites exhibited significant (p<0.05) regeneration of NA (69.6±12.0%) at 12 wk; trends for PDGF‐BB treatment effect were also observed in other parameters at 4 and 12 wk. although these increases were not statistically significant. Treatment with PDGF‐BB/IGF‐I resulted in 21.6±5.1 % and 42.5±8.3% ODF at 4 and 12 wk, respectively, and 64.1±7.7% and 74.6±7.4% NA at 4 and 12 wk, respectively (all significantly greater than vehicle, p<0.05). The results from this study demonstrated that: 1) IGF‐1 alone at the dose tested did not significantly alter periodontal wound healing; 2) PDGF‐BB alone significantly stimulated NA, with trends of effect on other parameters; and 3) the PDGF‐BB/IGF‐I combination resulted in significant increases in NA and ODF above vehicle at both 4 and 12 wk.
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Systemic growth hormone and locally administered insulin-like growth factor-I have been shown in a number of studies to improve the breaking strength of incisional wounds, especially in compromised animals. The objective of the present study was to compare these two agents when administered subcutaneously distant from an incisional wound site in pigs, as well as to examine effects of a combination growth hormone/insulin-like growth factor treatment. Growth hormone was shown to increase wound breaking strength in two experiments, whereas insulin-like growth factor-I or a more potent analog had no effect. Moreover, breaking strength was only minimally improved above the vehicle groups by the combination of growth hormone and insulin-like growth factor-I. These effects could not be explained by changes in plasma insulin-like growth factor-I concentrations which were highest in the combination groups, nor by plasma insulin-like growth factor binding protein-3 which was raised equally whenever growth hormone was administered. We conclude that systemic growth hormone but not insulin-like growth factor-I improves wound strength in normal pigs, whereas insulin-like growth factor-I reduces the magnitude of the growth hormone effect by an unknown mechanism.
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Human insulin-like growth factor 1 Ec (IGF-1Ec), also called mechano growth factor (MGF), is a splice variant of insulin-like growth factor 1 (IGF-1), which has been shown in vitro as well as in vivo to induce growth and hypertrophy in mechanically stimulated or damaged muscle. Growth, hypertrophy and responses to mechanical stimulation are important reactions of cartilaginous tissues, especially those in growth plates. Therefore, we wanted to ascertain if MGF is expressed in growth plate cartilage and if it influences proliferation of chondrocytes, as it does in musculoskeletal tissues. MGF expression was analyzed in growth plate and control tissue samples from piglets aged 3 to 6 weeks. Furthermore, growth plate chondrocyte cell culture was used to evaluate the effects of the MGF peptide on proliferation. We showed that MGF is expressed in considerable amounts in the tissues evaluated. We found the MGF peptide to be primarily located in the cytoplasm, and in some instances, it was also found in the nucleus of the cells. Addition of MGF peptides was not associated with growth plate chondrocyte proliferation.
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