目的探讨Rcan2在结直肠癌组织中的表达及与临床病理的相互关系。方法方便收集该院2012年1月—2017年1月期间诊治的炎症性肠病20例、增生性息肉20例、腺瘤40例、结直肠癌及其癌旁正常组织80例,获取标本总RNA,q PCR测定Rcan2 m RNA表达水...目的探讨Rcan2在结直肠癌组织中的表达及与临床病理的相互关系。方法方便收集该院2012年1月—2017年1月期间诊治的炎症性肠病20例、增生性息肉20例、腺瘤40例、结直肠癌及其癌旁正常组织80例,获取标本总RNA,q PCR测定Rcan2 m RNA表达水平,对Rcan2 m RNA的差异表达与结直肠癌患者临床病理信息进行相关性分析。体外转染Rcan2基因于结直肠癌colo320DM细胞,MTT实验观察Rcan2过表达对肿瘤细胞增殖的影响。体外转染kras突变基因(G12V)于人结直肠癌细胞中,观察Rcan2基因的表达情况。结果结直肠癌组织中Rcan2 m RNA表达量(2.98±0.21)明显高于其他各组。Rcan2 m RNA的表达量与肿瘤大小密切相关(P<0.01)。Rcan2-pcdna3.1转染的细胞增长速度慢,OD值从10上升到14,而pcdna3.1转染的细胞增长速度快,OD值从12上升到18,过表达kras(G12V)抑制Rcan2基因表达。Rcan2相对表达量从2.8下降到1.1。结论这些发现提示Rcan2是一个潜在的结直肠癌诊断指标。展开更多
体重及脂肪组织被认为受到能量稳态机制的严格调控,即脂肪细胞分泌的、显示机体脂肪含量的信号分子——瘦素通过下丘脑的信号通路对体重进行双向调控.近几十年来肥胖在全球暴发,肥胖个体中过量的瘦素并未抑制体重的增长,该现象被归因于&...体重及脂肪组织被认为受到能量稳态机制的严格调控,即脂肪细胞分泌的、显示机体脂肪含量的信号分子——瘦素通过下丘脑的信号通路对体重进行双向调控.近几十年来肥胖在全球暴发,肥胖个体中过量的瘦素并未抑制体重的增长,该现象被归因于"瘦素抵抗".然而最近有证据显示,肥胖发生过程中瘦素功能没有改变,瘦素抵抗不存在.因此体重是否受稳态调控存有争议.而本研究组发现一种依赖R c a n 2基因且不受瘦素抑制的增加摄食及体重的机制,伴有高脂肪食物时可导致体重快速增加进而产生肥胖,该发现可为肥胖的流行提供新的解释.展开更多
It is widely accepted that body weight and adipose mass are tightly regulated by homeostatic mechanisms, in which leptin plays a critical role through hypothalamic pathways, and obesity is a result of homeostatic diso...It is widely accepted that body weight and adipose mass are tightly regulated by homeostatic mechanisms, in which leptin plays a critical role through hypothalamic pathways, and obesity is a result of homeostatic disorder. However, in C57BL/6J mice, we found that Rcan2 increases food intake and plays an important role in the develop- ment of age- and diet-induced obesity through a leptin-independent mechanism. RCAN2 was initially identified as a thyroid hormone （T3）-responsive gene in human fibroblasts. Expression of RCAN2 is regulated by T3 through the PI3K-Akt/PKB-mTOR-Rps6kbl signaling pathway. Intriguingly, both Rcan2-/- and Rps6kb1-/- mutations were re- ported to result in lean phenotypes in mice. In this study we compared the effects of these two mutations on growth and body weight in C57BL/6J mice. We observed reduced body weight and lower fat mass in both Rcan2-/- and Rps6kb1-/- mice compared to the wild-type mice, and we reported other differences unique to either the Rcan2-/- or Rps6kb1-/- mice. Firstly, loss of Rcan2 does not directly alter body length; however, Rcan2-/- mice exhibit reduced food intake. In contrast, Rps6kb1-/- mice exhibit abnormal embryonic development, which leads to smaller body size and reduced food intake in adulthood. Secondly, when fed a normal chow diet, Rcan2-/- mice weigh significantly more than Rps6kb1-/- mice, but both Rcan2-/- and Rps6kbl-/- mice develop similar amounts of epididymal fat. On a high-fat diet, Rcan2-/- mice gain body weight and fat mass at slower rates than Rps6kb1-/- mice. Finally, using the double-knockout mice （Rcan2-/- Rps6kb1-/-）, we demonstrate that concurrent loss of Rcan2and Rps6kbl has an additive effect on body weight reduction in C57BL/6J mice. Our data suggest that Rcan2 and Rps6kbl mutations both affect growth and body weight of mice, though likely through different mechanisms.展开更多
文摘目的探讨Rcan2在结直肠癌组织中的表达及与临床病理的相互关系。方法方便收集该院2012年1月—2017年1月期间诊治的炎症性肠病20例、增生性息肉20例、腺瘤40例、结直肠癌及其癌旁正常组织80例,获取标本总RNA,q PCR测定Rcan2 m RNA表达水平,对Rcan2 m RNA的差异表达与结直肠癌患者临床病理信息进行相关性分析。体外转染Rcan2基因于结直肠癌colo320DM细胞,MTT实验观察Rcan2过表达对肿瘤细胞增殖的影响。体外转染kras突变基因(G12V)于人结直肠癌细胞中,观察Rcan2基因的表达情况。结果结直肠癌组织中Rcan2 m RNA表达量(2.98±0.21)明显高于其他各组。Rcan2 m RNA的表达量与肿瘤大小密切相关(P<0.01)。Rcan2-pcdna3.1转染的细胞增长速度慢,OD值从10上升到14,而pcdna3.1转染的细胞增长速度快,OD值从12上升到18,过表达kras(G12V)抑制Rcan2基因表达。Rcan2相对表达量从2.8下降到1.1。结论这些发现提示Rcan2是一个潜在的结直肠癌诊断指标。
文摘体重及脂肪组织被认为受到能量稳态机制的严格调控,即脂肪细胞分泌的、显示机体脂肪含量的信号分子——瘦素通过下丘脑的信号通路对体重进行双向调控.近几十年来肥胖在全球暴发,肥胖个体中过量的瘦素并未抑制体重的增长,该现象被归因于"瘦素抵抗".然而最近有证据显示,肥胖发生过程中瘦素功能没有改变,瘦素抵抗不存在.因此体重是否受稳态调控存有争议.而本研究组发现一种依赖R c a n 2基因且不受瘦素抑制的增加摄食及体重的机制,伴有高脂肪食物时可导致体重快速增加进而产生肥胖,该发现可为肥胖的流行提供新的解释.
基金Project supported by the National Natural Science Foundation of China(Nos.31140091 and 31371495)Shandong Natural Science Foundation(No.ZR2013CM040),China
文摘It is widely accepted that body weight and adipose mass are tightly regulated by homeostatic mechanisms, in which leptin plays a critical role through hypothalamic pathways, and obesity is a result of homeostatic disorder. However, in C57BL/6J mice, we found that Rcan2 increases food intake and plays an important role in the develop- ment of age- and diet-induced obesity through a leptin-independent mechanism. RCAN2 was initially identified as a thyroid hormone （T3）-responsive gene in human fibroblasts. Expression of RCAN2 is regulated by T3 through the PI3K-Akt/PKB-mTOR-Rps6kbl signaling pathway. Intriguingly, both Rcan2-/- and Rps6kb1-/- mutations were re- ported to result in lean phenotypes in mice. In this study we compared the effects of these two mutations on growth and body weight in C57BL/6J mice. We observed reduced body weight and lower fat mass in both Rcan2-/- and Rps6kb1-/- mice compared to the wild-type mice, and we reported other differences unique to either the Rcan2-/- or Rps6kb1-/- mice. Firstly, loss of Rcan2 does not directly alter body length; however, Rcan2-/- mice exhibit reduced food intake. In contrast, Rps6kb1-/- mice exhibit abnormal embryonic development, which leads to smaller body size and reduced food intake in adulthood. Secondly, when fed a normal chow diet, Rcan2-/- mice weigh significantly more than Rps6kb1-/- mice, but both Rcan2-/- and Rps6kbl-/- mice develop similar amounts of epididymal fat. On a high-fat diet, Rcan2-/- mice gain body weight and fat mass at slower rates than Rps6kb1-/- mice. Finally, using the double-knockout mice （Rcan2-/- Rps6kb1-/-）, we demonstrate that concurrent loss of Rcan2and Rps6kbl has an additive effect on body weight reduction in C57BL/6J mice. Our data suggest that Rcan2 and Rps6kbl mutations both affect growth and body weight of mice, though likely through different mechanisms.
