【目的】对藏羊BMP受体II(Bone morphogenetic protein receptor,type II,BMPRII)基因进行克隆和生物信息学分析,并检测其在藏羊不同组织中的表达差异,为研究BMPRII基因在藏羊中的生物学功能提供参考。【方法】本试验随机选取年龄和体...【目的】对藏羊BMP受体II(Bone morphogenetic protein receptor,type II,BMPRII)基因进行克隆和生物信息学分析,并检测其在藏羊不同组织中的表达差异,为研究BMPRII基因在藏羊中的生物学功能提供参考。【方法】本试验随机选取年龄和体重相近的6只藏羊进行屠宰,采集各组织样品,提取总RNA并进行质量检测,利用RT-qPCR检测BMPRII基因在藏羊下丘脑、垂体、心脏、肝脏、脾脏、肺脏、肾脏、卵巢、子宫、输卵管、瘤胃、十二指肠和背最长肌等13个组织中的表达量,分析BMPRII基因在藏羊各组织中的特异性表达和分布规律,并对藏羊BMPRII基因编码区序列进行克隆和测序,应用生物学软件对其基因编码产物进行生物信息学分析。【结果】BMPRII基因在上述13个组织中均有表达,在肝脏中的表达量高于子宫、卵巢和脾脏,未达到显著水平(P>0.05),但显著高于其他组织(P<0.05),在背最长肌中表达量最低。藏羊BMPRII基因CDS区序列长为3117 bp,编码1038个氨基酸。藏羊BMPRII氨基酸序列与绵羊、牛和牦牛的关系最近,与斑马和鸡的亲缘关系最远。藏羊BMPRII蛋白属于亲水性分泌蛋白,且具有不稳定性,含1个跨膜结构和信号肽,存在127个潜在的磷酸化位点、14个潜在的N-糖基化位点,主要分布在细胞外;藏羊BMPRII蛋白二级结构以无规卷曲为主,其次为α螺旋、延伸链和β转角,三级结构预测结果与二级结构一致。【结论】BMPRII基因在藏羊各项生理活动中发挥着重要作用,本研究结果可为进一步研究BMPRII基因对藏羊繁殖性能调控作用奠定基础。展开更多
动脉性肺动脉高压(Pulmonary Arterial Hypertension, PAH),即第1大类肺动脉高压,是一种以高发病率和死亡率为特点的血管疾病,其主要表现是肺血管重塑和肺血管阻力增加,最终导致右心室衰竭甚至死亡。骨形态发生蛋白9 (Bone Morphogeneti...动脉性肺动脉高压(Pulmonary Arterial Hypertension, PAH),即第1大类肺动脉高压,是一种以高发病率和死亡率为特点的血管疾病,其主要表现是肺血管重塑和肺血管阻力增加,最终导致右心室衰竭甚至死亡。骨形态发生蛋白9 (Bone Morphogenetic Protein 9, BMP9)属于转化生长因子β (Transforming Growth Factor-β, TGF-β)家族,主要由肝脏星状细胞产生,随血液循环到肺血管内皮细胞上与受体结合,在PAH中发挥相应的生物学效应,但是部分研究结果是相互矛盾的。本文对PAH中BMP9的信号通路及BMP9对肺血管内皮细胞作用的研究和进展进行综述。Arterial pulmonary hypertension (PAH), also known as the group 1 pulmonary hypertension, is a vascular disease characterized by high morbidity and mortality, and its main manifestations are pulmonary vascular remodeling and increased pulmonary vascular resistance, which eventually leads to right ventricular failure and even death. Bone Morphogenetic Protein 9 (BMP9) belongs to the Transforming Growth Factor-β (TGF-β) family, which is mainly produced by hepatic stellate cells, which circulates to pulmonary vascular endothelial cells with blood and bind to their receptors to exert corresponding biological effects in PAH, but some research results are contradictory. This article briefly reviews the BMP9 signaling pathway in PAH and the research and progress of BMP9 on pulmonary vascular endothelial cells.展开更多
Human telomerase reverse transcriptase （hTERT） plays a central role in telomere lengthening for continuous cell proliferation, but it remains unclear how extracellular cues regulate telomerase lengthening of telomer...Human telomerase reverse transcriptase （hTERT） plays a central role in telomere lengthening for continuous cell proliferation, but it remains unclear how extracellular cues regulate telomerase lengthening of telomeres. Here we report that the cytokine bone morphogenetic protein-7 （BMP7） induces the hTERT gene repression in a BMPRII receptor- and Smad3-dependent manner in human breast cancer cells. Chonic exposure of human breast cancer cells to BMP7 results in short telomeres, cell senescence and apoptosis. Mutation of the BMPRII receptor, but not TGFbRII, ACTRIIA or ACTRIIB receptor, inhibits BMP7-induced repression of the hTERT gene promoter activity, leading to increased telomerase activity, lengthened telomeres and continued cell proliferation. Expression of hTERT prevents BMP7-induced breast cancer cell senescence and apoptosis. Thus, our data suggest that BMP7 induces breast cancer cell aging by a mechanism involving BMPRII receptor- and Smad3-mediated repression of the hTERT gene.展开更多
文摘动脉性肺动脉高压(Pulmonary Arterial Hypertension, PAH),即第1大类肺动脉高压,是一种以高发病率和死亡率为特点的血管疾病,其主要表现是肺血管重塑和肺血管阻力增加,最终导致右心室衰竭甚至死亡。骨形态发生蛋白9 (Bone Morphogenetic Protein 9, BMP9)属于转化生长因子β (Transforming Growth Factor-β, TGF-β)家族,主要由肝脏星状细胞产生,随血液循环到肺血管内皮细胞上与受体结合,在PAH中发挥相应的生物学效应,但是部分研究结果是相互矛盾的。本文对PAH中BMP9的信号通路及BMP9对肺血管内皮细胞作用的研究和进展进行综述。Arterial pulmonary hypertension (PAH), also known as the group 1 pulmonary hypertension, is a vascular disease characterized by high morbidity and mortality, and its main manifestations are pulmonary vascular remodeling and increased pulmonary vascular resistance, which eventually leads to right ventricular failure and even death. Bone Morphogenetic Protein 9 (BMP9) belongs to the Transforming Growth Factor-β (TGF-β) family, which is mainly produced by hepatic stellate cells, which circulates to pulmonary vascular endothelial cells with blood and bind to their receptors to exert corresponding biological effects in PAH, but some research results are contradictory. This article briefly reviews the BMP9 signaling pathway in PAH and the research and progress of BMP9 on pulmonary vascular endothelial cells.
基金We thank Claude Labrie for the plasmid construct encoding BMPRII truncation and Peter Lansdorp for the TFL-Telo 2.2 software program for telomere analysis. This work was supported by grants from the National Basic Research Program （973 Program） （No. 2012CB911204）, National Natural Science Foundation of China （Grant Nos. 81170313 and 81272889）, the National Health and Medical Research Council of Australia and Australia Research Council. Cancer Council of Victoria, Australia.
文摘Human telomerase reverse transcriptase （hTERT） plays a central role in telomere lengthening for continuous cell proliferation, but it remains unclear how extracellular cues regulate telomerase lengthening of telomeres. Here we report that the cytokine bone morphogenetic protein-7 （BMP7） induces the hTERT gene repression in a BMPRII receptor- and Smad3-dependent manner in human breast cancer cells. Chonic exposure of human breast cancer cells to BMP7 results in short telomeres, cell senescence and apoptosis. Mutation of the BMPRII receptor, but not TGFbRII, ACTRIIA or ACTRIIB receptor, inhibits BMP7-induced repression of the hTERT gene promoter activity, leading to increased telomerase activity, lengthened telomeres and continued cell proliferation. Expression of hTERT prevents BMP7-induced breast cancer cell senescence and apoptosis. Thus, our data suggest that BMP7 induces breast cancer cell aging by a mechanism involving BMPRII receptor- and Smad3-mediated repression of the hTERT gene.
