Effects of vitamin D3 stimulation of thioredoxin-interacting protein in hepatocellular carcinoma.
Effects of vitamin D3 stimulation of thioredoxin-interacting protein in hepatocellular carcinoma.
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DOI：
10.1111/hepr.12302
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发表时间：
2014-12
期刊：
影响因子：
--
通讯作者：
Mezey E
中科院分区：
文献类型：
--
作者：
Hamilton JP;Potter JJ;Koganti L;Meltzer SJ;Mezey E
硫氧还蛋白相互作用蛋白（TXNIP）通过灭活硫氧还蛋白（TXN）促进氧化应激。这种蛋白参与多种疾病过程，包括胰岛素抵抗、动脉粥样硬化和癌变。本研究的目的是测量TXNIP在体外肝脏疾病模型以及原发性人肝细胞癌（HCC）组织标本中的表达和功能。此外，我们想确定维生素d3诱导的TXNIP刺激对hcc来源细胞系的影响。采用定量逆转录聚合酶链反应和western blot检测TXNIP的表达。维生素D暴露和转染均可刺激TXNIP的表达。用标准法测定细胞增殖、凋亡和活性氧含量。TXNIP在HCC细胞系中的表达水平较低，维生素D3可刺激TXNIP在体外的表达。在转染TXNIP表达载体或外源性维生素D3处理的HCC细胞中，细胞增殖减少，细胞凋亡增加。表达TXNIP的细胞对氯化钴或细菌脂多糖诱导的氧化损伤明显敏感。与匹配的非癌性肝组织相比，大多数原发性人HCC标本中TXNIP的表达减少或缺失。TXNIP在人类HCC标本和HCC衍生细胞系中表达低或不表达。维生素D3刺激TXNIP的表达，导致细胞增殖减少，细胞凋亡增加。表达TXNIP的肝细胞可引发氧化损伤。这些发现表明，通过维生素D3等因素刺激TXNIP的表达，可能会减轻慢性肝病患者的癌变。
Thioredoxin-interacting protein (TXNIP) promotes oxidative stress by inactivating thioredoxin (TXN). This protein is involved in diverse disease processes, including insulin resistance, atherosclerosis and carcinogenesis. The aim of the present study was to measure the expression and function of TXNIP in in vitro models of liver disease, as well as in primary human hepatocellular carcinoma (HCC) tissue specimens. In addition, we wanted to determine the effects of vitamin D3-induced TXNIP stimulation in HCC-derived cell lines. TXNIP expression was measured by quantitative reverse transcription polymerase chain reaction and western blots. TXNIP expression was stimulated by vitamin D exposure and by transfection. Cell proliferation, apoptosis and reactive oxygen species were determined by standard assays. TXNIP expression levels were low in HCC cell lines, and vitamin D3 stimulated TXNIP expression in vitro. In HCC cells transfected with a TXNIP expression vector or treated with exogenous vitamin D3, there was a reduction in cell proliferation and an increase in apoptosis. Cells expressing TXNIP were markedly susceptible to oxidative injury induced by cobalt chloride or bacterial lipopolysaccharide. TXNIP expression was reduced or absent in a majority of primary human HCC specimens relative to matching, non-cancerous liver tissue. TXNIP expression is low or absent in human HCC specimens and HCC-derived cell lines. Vitamin D3 stimulates TXNIP expression, resulting in diminished proliferation and enhanced apoptosis. Liver cells expressing TXNIP are primed for oxidative injury. These findings suggest that stimulation of TXNIP expression, by factors such as vitamin D3, may attenuate carcinogenesis in patients with chronic liver disease.
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DOI：
10.1016/j.biocel.2011.09.005
发表时间：
2011-12-01
影响因子：
4
作者：
Zhou, Jianbiao;Yu, Qiang;Chng, Wee-Joo
通讯作者：
Chng, Wee-Joo
影响因子：
7.4
作者：
Marra M;Sordelli IM;Lombardi A;Lamberti M;Tarantino L;Giudice A;Stiuso P;Abbruzzese A;Sperlongano R;Accardo M;Agresti M;Caraglia M;Sperlongano P
通讯作者：
Sperlongano P
影响因子：
11.2
作者：
Jeon, JH;Lee, KN;Choi, I
通讯作者：
Choi, I
影响因子：
11.2
作者：
Nishinaka, Y;Nishiyama, A;Yodoi, J
通讯作者：
Yodoi, J
DOI：
10.1111/liv.12122
发表时间：
2013-05
期刊：
Liver international : official journal of the International Association for the Study of the Liver
影响因子：
--
作者：
Potter JJ;Liu X;Koteish A;Mezey E
通讯作者：
Mezey E