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
目的探讨孕妇血清胰岛素样生长因子1(insulin like growth factor 1,IGF-1)、IGF-2、IGF结合蛋白3(IGF binding protein 3,IGFBP-3)与正常胎儿生长的关系。方法选择2010年1月至2011年5月于上海市浦东新区人民医院产前检查并分娩正常体...目的探讨孕妇血清胰岛素样生长因子1(insulin like growth factor 1,IGF-1)、IGF-2、IGF结合蛋白3(IGF binding protein 3,IGFBP-3)与正常胎儿生长的关系。方法选择2010年1月至2011年5月于上海市浦东新区人民医院产前检查并分娩正常体重儿的初产妇66例,分为妊娠16～18周、妊娠26～28周、妊娠37～40周3个阶段进行纵向观察,放射免疫法测定孕妇各阶段血清中IGF-1、IGF-2、IGFBP-3水平并进行对比分析。结果孕期母血IGF-1水平随着孕周增加明显上升,其中IGF-1水平在妊娠37～40周高于妊娠26～28周,妊娠26～28周高于妊娠16～18周,差异均有显著统计学意义(P均<0.01)。孕期母血IGF-2水平随孕周增加无明显改变,妊娠3阶段差异无统计学意义(P>0.05)。母血IGFBP-3水平妊娠37～40周高于妊娠26～28周及妊娠16～18周期,差异有统计学意义(P<0.05),而妊娠26～28周与妊娠16～18周无显著差异。妊娠16～18周、26～28周和37～40周3阶段母血IGF-1、IGF-2、IGFBP-3水平与正常新生儿出生体重无显著相关性。结论孕妇血清IGF-1、IGFBP-3水平与正常胎儿生长密切相关,IGF-1可作为临床评价不同阶段正常胎儿生长的指标,而IGFBP-3更多地反映了妊娠中晚期正常胎儿的生长。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.
文摘目的探讨孕妇血清胰岛素样生长因子1(insulin like growth factor 1,IGF-1)、IGF-2、IGF结合蛋白3(IGF binding protein 3,IGFBP-3)与正常胎儿生长的关系。方法选择2010年1月至2011年5月于上海市浦东新区人民医院产前检查并分娩正常体重儿的初产妇66例,分为妊娠16～18周、妊娠26～28周、妊娠37～40周3个阶段进行纵向观察,放射免疫法测定孕妇各阶段血清中IGF-1、IGF-2、IGFBP-3水平并进行对比分析。结果孕期母血IGF-1水平随着孕周增加明显上升,其中IGF-1水平在妊娠37～40周高于妊娠26～28周,妊娠26～28周高于妊娠16～18周,差异均有显著统计学意义(P均<0.01)。孕期母血IGF-2水平随孕周增加无明显改变,妊娠3阶段差异无统计学意义(P>0.05)。母血IGFBP-3水平妊娠37～40周高于妊娠26～28周及妊娠16～18周期,差异有统计学意义(P<0.05),而妊娠26～28周与妊娠16～18周无显著差异。妊娠16～18周、26～28周和37～40周3阶段母血IGF-1、IGF-2、IGFBP-3水平与正常新生儿出生体重无显著相关性。结论孕妇血清IGF-1、IGFBP-3水平与正常胎儿生长密切相关,IGF-1可作为临床评价不同阶段正常胎儿生长的指标,而IGFBP-3更多地反映了妊娠中晚期正常胎儿的生长。
