OBJECTIVE Basic fibroblast growth factor(b FGF)and platelet-derived growth factor(PDGF)produced by hepatocellular carcinoma(HCC)cells are responsible for the cell growth.Accumulating evidence shows that insulin-like g...OBJECTIVE Basic fibroblast growth factor(b FGF)and platelet-derived growth factor(PDGF)produced by hepatocellular carcinoma(HCC)cells are responsible for the cell growth.Accumulating evidence shows that insulin-like growth factor-binding protein-3(IGFBP-3)suppresses HCC cell proliferation in both IGF-dependent and independent manners.The present study is to investigate whether treatment with exogenous IGFBP-3 inhibits bF GF and PDGF production and the cell proliferation of HCC cells.METHODS Cell Counting Kit 8 assay were designed to detect HCC cell proliferation,transcription factor early growth response-1(EGR1)involving in IGFBP-3 regulation of b FGF and PDGF were detected by RT-PCR and Western blot assays.Western blot assay was adopted to detect the IGFBP-3 regulating insulin-like growth factor 1 receptor(IGF-1R)signaling pathway.RESULTS The present study demonstrates that IGFBP-3 suppressed IGF-1-induced b FGF and PDGF expression while it does not affect their expression in the absence of IGF-1.To delineate the underlying mechanism,Western-blot and RT-PCR assays confirmed that the transcription factor early growth response protein 1(EGR1)is involved in IGFBP-3 regulation of b FGF and PDGF.IGFBP-3 inhibition of type 1 insulin-like growth factor receptor(IGF1R),ERK and AKT activation is IGF-1-dependent.Furthermore,transient transfection with constitutively activated AKT or MEK partially blocks the IGFBP-3 inhibition of EGR1,b FGF and PDGF expression.CONCLUSION In conclusion,these findings suggest that IGFBP-3suppresses transcription of EGR1 and its target genes b FGF and PDGF through inhibiting IGF-1-dependent ERK and AKT activation.It demonstrates the importance of IGFBP-3 in the regulation of HCC cell proliferation,suggesting that IGFBP-3 could be a target for the treatment of HCC.展开更多
In recent years,growth hormone and insulin-like growth factors have become key regulators of bone metabolism and remodeling,crucial for maintaining healthy bone mass throughout life.Studies have shown that adult growt...In recent years,growth hormone and insulin-like growth factors have become key regulators of bone metabolism and remodeling,crucial for maintaining healthy bone mass throughout life.Studies have shown that adult growth hormone deficiency leads to alterations in bone remodeling,significantly affecting bone microarchitecture and increasing fracture risk.Although recombinant human growth hormone replacement therapy can mitigate these adverse effects,improving bone density,and reduce fracture risk,its effectiveness in treating osteoporosis,especially in adults with established growth hormone deficiency,seems limited.Bisphosphonates inhibit bone resorption by targeting farnesyl pyrophosphate synthase in osteoclasts,and clinical trials have confirmed their efficacy in improving osteoporosis.Therefore,for adult growth hormone deficiency patients with osteoporosis,the use of bisphosphonates alongside growth hormone replacement therapy is recommended.展开更多
目的观察血小板衍生生长因子-BB(PDGF-BB)与胰岛素样生长因子-Ⅰ(IGF-Ⅰ)联合应用对大鼠正畸牙压力侧牙周膜细胞(PDLCs)中整合素β3蛋白表达的影响。方法建立SD大鼠正畸牙移动模型,隔日于正畸牙颊侧牙龈黏膜下单独或联合注射10 ng PDGF...目的观察血小板衍生生长因子-BB(PDGF-BB)与胰岛素样生长因子-Ⅰ(IGF-Ⅰ)联合应用对大鼠正畸牙压力侧牙周膜细胞(PDLCs)中整合素β3蛋白表达的影响。方法建立SD大鼠正畸牙移动模型,隔日于正畸牙颊侧牙龈黏膜下单独或联合注射10 ng PDGF-BB及200 ng IGF-Ⅰ,加力10 d后处死大鼠,取材用免疫组织化学方法检测正畸牙压力侧牙周膜细胞中整合素β3的表达。结果 PDGF-BB、IGF-Ⅰ单独或联合应用均能增强压力侧牙周膜细胞中整合素β3表达(P<0.01);与PDGF-BB、IGF-Ⅰ单独应用比较,IGF-Ⅰ加PDGF-BB组牙周膜细胞中整合素β3表达明显增强(P<0.05和P<0.01)。结论外源性PDGF-BB和IGF-Ⅰ在大鼠正畸牙的局部注射能上调压力侧牙周膜细胞中整合素β3表达,二者联合应用具有协同效应。展开更多
基金supported by National Natural Science Foundation of China(81502123 and81330081)Natural Science Foundation of Anhui Province(1308085QH130)Anhui Province Nature Science Foundation in University(KJ2014A119)
文摘OBJECTIVE Basic fibroblast growth factor(b FGF)and platelet-derived growth factor(PDGF)produced by hepatocellular carcinoma(HCC)cells are responsible for the cell growth.Accumulating evidence shows that insulin-like growth factor-binding protein-3(IGFBP-3)suppresses HCC cell proliferation in both IGF-dependent and independent manners.The present study is to investigate whether treatment with exogenous IGFBP-3 inhibits bF GF and PDGF production and the cell proliferation of HCC cells.METHODS Cell Counting Kit 8 assay were designed to detect HCC cell proliferation,transcription factor early growth response-1(EGR1)involving in IGFBP-3 regulation of b FGF and PDGF were detected by RT-PCR and Western blot assays.Western blot assay was adopted to detect the IGFBP-3 regulating insulin-like growth factor 1 receptor(IGF-1R)signaling pathway.RESULTS The present study demonstrates that IGFBP-3 suppressed IGF-1-induced b FGF and PDGF expression while it does not affect their expression in the absence of IGF-1.To delineate the underlying mechanism,Western-blot and RT-PCR assays confirmed that the transcription factor early growth response protein 1(EGR1)is involved in IGFBP-3 regulation of b FGF and PDGF.IGFBP-3 inhibition of type 1 insulin-like growth factor receptor(IGF1R),ERK and AKT activation is IGF-1-dependent.Furthermore,transient transfection with constitutively activated AKT or MEK partially blocks the IGFBP-3 inhibition of EGR1,b FGF and PDGF expression.CONCLUSION In conclusion,these findings suggest that IGFBP-3suppresses transcription of EGR1 and its target genes b FGF and PDGF through inhibiting IGF-1-dependent ERK and AKT activation.It demonstrates the importance of IGFBP-3 in the regulation of HCC cell proliferation,suggesting that IGFBP-3 could be a target for the treatment of HCC.
基金This work was supported by the Special Project of Performance Incentive and Guidance for Scientific Research Institutions of Chongqing,China (jxyn2022-5)。
文摘In recent years,growth hormone and insulin-like growth factors have become key regulators of bone metabolism and remodeling,crucial for maintaining healthy bone mass throughout life.Studies have shown that adult growth hormone deficiency leads to alterations in bone remodeling,significantly affecting bone microarchitecture and increasing fracture risk.Although recombinant human growth hormone replacement therapy can mitigate these adverse effects,improving bone density,and reduce fracture risk,its effectiveness in treating osteoporosis,especially in adults with established growth hormone deficiency,seems limited.Bisphosphonates inhibit bone resorption by targeting farnesyl pyrophosphate synthase in osteoclasts,and clinical trials have confirmed their efficacy in improving osteoporosis.Therefore,for adult growth hormone deficiency patients with osteoporosis,the use of bisphosphonates alongside growth hormone replacement therapy is recommended.
文摘目的观察血小板衍生生长因子-BB(PDGF-BB)与胰岛素样生长因子-Ⅰ(IGF-Ⅰ)联合应用对大鼠正畸牙压力侧牙周膜细胞(PDLCs)中整合素β3蛋白表达的影响。方法建立SD大鼠正畸牙移动模型,隔日于正畸牙颊侧牙龈黏膜下单独或联合注射10 ng PDGF-BB及200 ng IGF-Ⅰ,加力10 d后处死大鼠,取材用免疫组织化学方法检测正畸牙压力侧牙周膜细胞中整合素β3的表达。结果 PDGF-BB、IGF-Ⅰ单独或联合应用均能增强压力侧牙周膜细胞中整合素β3表达(P<0.01);与PDGF-BB、IGF-Ⅰ单独应用比较,IGF-Ⅰ加PDGF-BB组牙周膜细胞中整合素β3表达明显增强(P<0.05和P<0.01)。结论外源性PDGF-BB和IGF-Ⅰ在大鼠正畸牙的局部注射能上调压力侧牙周膜细胞中整合素β3表达,二者联合应用具有协同效应。
