• The Korean Journal of Physiology and Pharmacology
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• 제19권6호
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• pp.499-506
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• 2015

Angiotensin II (Ang II), a key mediator of hypertensive, causes structural changes in the arteries (vascular remodeling), which involve alterations in cell growth, vascular smooth muscle cell (VSMC) hypertrophy. Ang II promotes fibrotic factor like IGFBP5, which mediates the profibrotic effects of Ang II in the heart and kidneys, lung and so on. The purpose of this study was to identify the signaling pathway of IGFBP5 on cell proliferation and migration of Ang II-stimulated VSMC. We have been interested in Ang II-induced IGFBP5 and were curious to determine whether a Pitavastatin would ameliorate the effects. Herein, we investigated the question of whether Ang II induced the levels of IGFBP5 protein followed by proliferation and migration in VSMC. Pretreatment with the specific Angiotensin receptor type 1 (AT1) inhibitor (Losartan), Angiotensin receptor type 2 (AT2) inhibitor (PD123319), MAPK inhibitor (U0126), ERK1/2 inhibitor (PD98059), P38 inhibitor (SB600125) and PI3K inhibitor (LY294002) resulted in significantly inhibited IGFBP5 production, proliferation, and migration in Ang II-stimulated VSMC. In addition, IGFBP5 knockdown resulted in modulation of Ang II induced proliferation and migration via IGFBP5 induction. In addition, Pitavastatin modulated Ang II induced proliferation and migration in VSMC. Taken together, our results indicated that Ang II induces IGFBP5 through AT1, ERK1/2, P38, and PI3K signaling pathways, which were inhibited by Pitavastatin. These findings may suggest that Pitavastatin has an effect on vascular disease including hypertension.

• Asian Pacific Journal of Cancer Prevention
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• 제15권14호
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• pp.5741-5745
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• 2014

Purpose: To study the expression of insulin-like growth factor binding proteins (IGFBPs) in paclitaxel-treated gastric cancer SGC-7901 cells, and to further investigate underlying mechanisms. Materials and Methods: Real time PCR and Western blot assays were applied to detect the mRNA and protein expression of IGFBP-2, -3 and -5 after paclitaxel (10 nM) treatment of SGC-7901 cells. In addition IGFBP-3 expression was silenced by RNA interference to determine effects. Cell viability was determined by MTT assay. Cell cycling and apoptosis were assessed by flow cytometry. Results: Compared to the control group, only IGFBP-3 expression was elevated significantly after paclitaxel (10 nM) treatment (p<0.05). Paclitaxel treatment caused cell cycle arrest and apoptosis via downregulating Bcl-2 expression. However, the effect could be abrogated by IGFBP-3 silencing. Conclusions: IGFBP-3 exhibits anti-apoptotic effects on paclitaxel-treated SGC-7901 cells via elevating Bcl-2 expression.

• Journal of Periodontal and Implant Science
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• 제52권2호
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• pp.155-169
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• 2022

Purpose: The aim of this study was to determine the effect of insulin growth factor binding protein-3 (IGFBP-3) on the inhibition of glucose oxidative stress and promotion of bone formation near the implant site in a rat model of methylglyoxal (MGO)-induced bone loss. Methods: An in vitro study was performed in MC3T3 E1 cells treated with chitosan gold nanoparticles (Ch-GNPs) conjugated with IGFBP-3 cDNA followed by MGO. An in vivo study was conducted in a rat model induced by MGO administration after the insertion of a dental implant coated with IGFBP-3. Results: MGO treatment downregulated molecules involved in osteogenic differentiation and bone formation in MC3T3 E1 cells and influenced the bone mineral density and bone volume of the femur and alveolar bone. In contrast, IGFBP-3 inhibited oxidative stress and inflammation and enhanced osteogenesis in MGO-treated MC3T3 E1 cells. In addition, IGFBP-3 promoted bone formation by reducing inflammatory proteins in MGO-administered rats. The application of Ch-GNPs conjugated with IGFBP-3 as a coating of titanium implants enhanced osteogenesis and the osseointegration of dental implants. Conclusions: This study demonstrated that IGFBP-3 could be applied as a therapeutic component in dental implants to promote the osseointegration of dental implants in patients with diabetes, which affects MGO levels.

• 생명과학회지
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• 제17권5호
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• pp.687-693
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• 2007

사람의 섬유아세포인 GM10을 사용하여 glucose의 배양조건에 다른 물질대사 및 IGFBP-3 발현을 살펴본 결과, glucose 농도에 따른 glucose 소비와 triglyceride 축적 수준은 고농도 glucose 배양 조건에서 증가한 반면, 총 단백질 함량은 고농도 glucose배양 조건에서 시간의 경과에 따라 감소하였다. 또한 고농도 glucose 배양 조건에서 5일 동안 배양한 세포 배양액내의 유리아미노산 함량은 저농도보다 고농도 glucose 배양 조건에서 높게 나타났다. IGFBP-3 단백질 수준과 mRNA수준은 저농도 glucose배양 조건에서 증가하였으나, IGFBP-3 단백질 분해효소에 따른 영향은 없었다. 이상의 결과에서 glucose 배양조건에 따른 물질대사는 부분적으로 세포를 이용한 당뇨병 모델 실험에서 in vivo와 같은 결과를 얻지 못하였지만, IGFs와 같은 세포 성장인자에 대한 연구를 통해 세포수준의 당뇨병 모델화가 가능하다고 여겨진다.

• Asian-Australasian Journal of Animal Sciences
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• 제14권3호
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• pp.307-315
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• 2001

Litter size has been one of the important economic traits in porcine reproduction. The insulin-like growth factor (IGF) system has been shown to mediate actions of the steroid hormone or to synergize with other endocrine factors so that it consequently plays roles in reproductive processes, including ovulation, implantation, maintenance of pregnancy, and fetal development. However, the effect of the serum IGF system on porcine litter size has not been deeply studied. Therefore, this study was conducted to relate serum IFG-II concentration and IGF binding protein-3 (IGFBP-3) expression with porcine litter size. Moreover, the possible association of those with estrogen receptor (ER) as a candidate gene for litter size was investigated. Swine were separated into two groups showing high and low litter sizes, and sera were collected from sows in the estrous cycle to postnatal growth of their female progeny. Serum IFG-II concentration was measured by radioimmunoassay and IGFBP-3 expression was detected by Western ligand blotting. During the estrous cycle, IGFBP-3 expression in both groups decreased moderately from metestrus to estrus, but IFG-II concentration showed a reverse pattern. Also, IFG-II concentration and IGFBP-3 expression decreased gradually as pregnancy proceeded. Unlike IGFBP-3, IFG-II decreased moderately as newborn pigs grew. Significant differences in serum IFG-II amount between the two groups were detected at 60 (p<0.01), 75, 90, and 105 d (p<0.05) of pregnancy and at 60 (p<0.01), 45, and 105 d (p<0.05) of postnatal growth. Furthermore, based on ER genotypes, a high litter size group with genotypes AB and BB showed lower IFG-II concentration than a low litter size group with a genotype AA during pregnancy. Taken together, the results indicate that the serum IFG-II and IGFBP-3 are correlated with the litter size in pigs.

• The Korean Journal of Physiology and Pharmacology
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• 제17권2호
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• pp.157-162
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• 2013

Insulin-like growth factor binding proteins (IGFBPs) are important components of insulin growth factor (IGF) signaling pathways. One of the binding proteins, IGFBP-5, enhances the actions of IGF-1, which include the enhanced proliferation of smooth muscle cells. In the present study, we examined the expression and the biological effects of IGFBP-5 in vascular smooth muscle cells (VSMCs) from spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY). The levels of IGFBP-5 mRNA and protein were found to be higher in the VSMC from SHR than in those from WKY. Treatment with recombinant IGFBP-5-stimulated VSMC proliferation in WKY to the levels observed in SHR. In the VSMCs of WKY, incubation with angiotensin (Ang) II or IGF-1 dose dependently increased IGFBP-5 protein levels. Transfection with IGFBP-5 siRNA reduced VSMC proliferation in SHR to the levels exhibited in WKY. In addition, recombinant IGFBP-5 significantly up-regulated ERK1/2 phosphorylation in the VSMCs of WKY as much as those of SHR. Concurrent treatment with the MEK1/2 inhibitors, PD98059 or U0126 completely inhibited recombinant IGFBP-5-induced VSMC proliferation in WKY, while concurrent treatment with the phosphatidylinositol-3 kinase inhibitor, LY294002, had no effect. Furthermore, knockdown with IGFBP-5 siRNA inhibited ERK1/2 phosphorylation in VSMC of SHR. These results suggest that IGFBP-5 plays a role in the regulation of VSMC proliferation via ERK1/2 MAPK signaling in hypertensive rats.

• Asian-Australasian Journal of Animal Sciences
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• 제25권11호
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• pp.1515-1520
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• 2012

Insulin-like growth factor binding protein-3 (IGFBP-3) gene is important for regulation of growth and development in mammals. The present investigation was carried out to study DNA polymorphism by PCR-RFLP of IGFBP-3 gene and its effect on fibre traits of Chinese Inner Mongolian cashmere goats. The fibre traits data investigated were cashmere fibre diameter, combed cashmere weight, cashmere fibre length and guard hair length. Four hundred and forty-four animals were used to detect polymorphisms in the hircine IGFBP-3 gene. A 316-bp fragment of the IGFBP-3 gene in exon 2 was amplified and digested with HaeIII restriction enzyme. Three patterns of restriction fragments were observed in the populations. The frequency of AA, AB and BB genotypes was 0.58, 0.33 and 0.09 respectively. The allelic frequency of the A and B allele was 0.75 and 0.25 respectively. Nucleotide sequencing revealed a C>G transition in the exon 2 region of the IGFBP-3 gene resulting in R158G change which caused the polymorphism. Least squares analysis revealed a significant effect of genotypes on cashmere weight (p<0.0001), cashmere fibre length (p<0.001) and hair length (p<0.05) of the animals. The effect of genotypes on cashmere fibre diameter was not statistically significant (p>0.05). The animals of AB and BB genotypes showed higher cashmere weight, cashmere fibre length and hair length than the animals possessing AA genotype. These results suggested that polymorphisms in the hircine IGFBP-3 gene might be a potential molecular marker for cashmere weight in cashmere goats.

• Molecules and Cells
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• 제42권4호
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• pp.321-332
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• 2019

The brain is the most common metastatic site of lung adenocarcinoma; however, the mechanism of this selective metastasis remains unclear. We aimed to verify the hypothesis that exposure of tumor cells to the brain microenvironment leads to changes in their gene expression, which promotes their oriented transfer to the brain. A549 and H1299 lung adenocarcinoma cells were exposed to human astrocyte-conditioned medium to simulate the brain microenvironment. Microarray analysis was used to identify differentially expressed genes, which were confirmed by quantitative real-time PCR and western blotting. Knockdown experiments using microRNAs and the overexpression of genes by cell transfection were performed in addition to migration and invasion assays. In vitro findings were confirmed in clinical specimens using immunohistochemistry. We found and confirmed a significant increase in insulin-like growth factor binding protein-3 (IGFBP3) levels. Our results also showed that the up-regulation of IGFBP3 promoted A549 cell epithelial-mesenchymal transition, migration, and invasion, while the knockdown of IGFBP3 resulted in decreased cell motility. We also found that Transforming growth factor-${\beta}$ (TGF-${\beta}$)/Mothers against decapentaplegic homolog 4 (Smad4)-induced epithelial-mesenchymal transition was likely IGFBP3-dependent in A549 cells. Finally, expression of IGFBP3 was significantly elevated in pulmonary cancer tissues and intracranial metastatic tissues. Our data indicate that up-regulation of IGFBP3 might mediate brain metastasis in lung adenocarcinoma, which makes it a potential therapeutic target.

• Asian Pacific Journal of Cancer Prevention
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• 제14권12호
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• pp.7427-7431
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• 2013

Aims: To examine the pretreatment effects of regular aerobic training on the IGF system (IGF-I, IGFBP-3 and IGF/IGFBP) and doxorubicin(DOX) induced hepatotoxicity in rats. Materials and Methods: Forty-eight male rats were divided into groups:(1) control+placebo (2) $control+DOX_{10}mg{\cdot}kg^{-1}$ (3) $control+DOX_{20}mg{\cdot}kg^{-1}$ (4) training+placebo (5) $training+DOX_{10}mg{\cdot}kg^{-1}$ (6) $training+DOX_{20}mg{\cdot}kg^{-1}$. Hepatotoxicity was induced by DOX with dosages of 10 and 20 $mg{\cdot}kg^{-1}$. The rats in groups 4, 5 and 6 performed treadmill running of 25-54 min/day and 15-20 m/min, 5 days/wk for 6 wks. At the end of the aerobic training protocol, rats in the 1 and 4 groups, in the 2 and 5 groups and in the 3 and 6 groups received saline solution, $DOX_{10}mg{\cdot}kg^{-1}$ and $DOX_{20}mg{\cdot}kg^{-1}$, respectively. Results: Administration of $DOX_{20}mg{\cdot}kg^{-1}$ caused a significant increase in IGF-1 and IGF-1/IGFBP-3, an insignificant decrease in IGFBP-3, as compared to the control+placebo group. However, after six weeks of aerobic training and DOX treatment with $10mg{\cdot}kg^{-1}$ and or/ $20mg{\cdot}kg^{-1}$ an insignificant decrease in IGF-1, an insignificant increase in IGFBP-3 and a significant decrease in IGF-1/IGFBP-3 were detected, in comparison to $C+DOX_{10}$ and $C+DOX_{20}$. Conclusions: Hepatotoxicity of doxorubicin is dose-dependent and pretreatment with regular aerobic training may improve DOX-induced hepatotoxicity by up-regulation of IGFBP3.

• 한국임상수의학회지
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• 제20권3호
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• pp.263-273
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• 2003

본 연구는 흰쥐의 난소제거로 유발한 골다공증에 대한 흥화씨(Carhamus inctorius L)의 투여 효과를 알아보기 위하여 혈청내 호르몬과 골소주의 변화를 관찰하였다 실험동물은 4개월 령의 흰쥐를 난소절제를 실시하여 골다공증을 유발 시킨 후 실험에 이용하였으며 30일간 격일 간격으로 0.03g/kg의 용량을 투여 하였다. 혈청 내에서 Insulin-like Growth Factors, Insulin-like Growth Factor binding protein-3 (IGFBP-3), Estrogen, Bone-specific alkaline phosphotase, Calcium, and Phospotase를 매 10일 간격으로 측정하였으며 비골의 골간을 채취하여 조직 형태학적인 검사를 실시하였고 체중에 대한 대퇴골 무게를 측정하였다. 홍화씨 투여 10일과 20일에서는 혈청내 IGF-I, IGF-II그리고 IGFBP-3의 변화는 대조군에 비하여 유의성 있는 변화를 관찰할 수 없었으나 홍화씨 투여 30일에 있어서는 IGF-I, IGF-II그리고 IGFBP-3의 변화가 대조군에 비하여 현저히 높은 유의서 있는 변화를 관찰할 수 있었다(p<0.05). Bone alkaline phosphatase(BALP)에 있어서도 홍화씨 투여 30일 에 가장 많은 변화가 있었으나 estrogen과 체중에 대한 대퇴골의 무게에 있어서는 유의성 있는 변화를 관찰하지 못했다. 오히려 이시기에 난소를 절제하지 않는 대조군의 estrogen치가 높게 나타났다. 난소절제로 골다공증을 유발시킨 흰쥐에 있어서 흥화씨의 투여는 혈청내 IGFs, IGFBP-3 and BALP을 높임으로서 골다공증 치료에 효과가 있는 것으로 사료됩니다.