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血清胰岛素样生长因子结合蛋白1作为早期酒精性肝病诊断生物标志物的鉴定

Identification of serum insulin-like growth factor binding protein 1 as diagnostic biomarker for early-stage alcohol-induced liver disease.

作者信息

Li Heng-Hong, Doiron Kathryn, Patterson Andrew D, Gonzalez Frank J, Fornace Albert J

机构信息

Department of Biochemistry and Molecular & Cellular Biology, Georgetown University, 3970 Reservoir Road, NW, New Research Building, Room E504, Washington, DC 20057, USA.

出版信息

J Transl Med. 2013 Oct 23;11:266. doi: 10.1186/1479-5876-11-266.

DOI:10.1186/1479-5876-11-266
PMID:24152801
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4016206/
Abstract

BACKGROUND

Alcohol consumption is a major cause of liver disease in humans. The use and monitoring of biomarkers associated with early, pre-clinical stages of alcohol-induced liver disease (pre-ALD) could facilitate diagnosis and treatment, leading to improved outcomes.

METHODS

We investigated the pathological, transcriptomic and protein changes in early stages of pre-ALD in mice fed the Lieber-Decarli liquid diet with or without alcohol for four months to identify biomarkers for the early stage of alcohol induced liver injury. Mice were sampled after 1, 2 and 4 months treatment.

RESULTS

Pathological examination revealed a modest increase in fatty liver changes in alcohol-treated mice. Transcriptomics revealed gene alterations at all time points. Most notably, the Igfbp1 (Insulin-Like Growth Factor Binding Protein 1) was selected as the best candidate gene for early detection of liver damage since it showed early and continuously enhanced induction during the treatment course. Consistent with the microarray data, both Igfbp1mRNA expression in the liver tissue and the IGFBP1 serum protein levels showed progressive and significant increases over the course of pre-ALD development.

CONCLUSIONS

The results suggest that in conjunction with other tests, serum IGFBPI protein could provide an easily measured biomarker for early detection of alcohol-induced liver injury in humans.

摘要

背景

饮酒是人类肝脏疾病的主要病因。使用和监测与酒精性肝病（ALD）临床前期早期阶段相关的生物标志物有助于诊断和治疗，从而改善治疗效果。

方法

我们研究了喂食含或不含酒精的Lieber-Decarli液体饮食四个月的小鼠在ALD临床前期早期阶段的病理、转录组和蛋白质变化，以确定酒精性肝损伤早期阶段的生物标志物。在治疗1、2和4个月后对小鼠进行采样。

结果

病理检查显示，酒精处理的小鼠脂肪肝变化略有增加。转录组学显示在所有时间点均有基因改变。最值得注意的是，胰岛素样生长因子结合蛋白1（Igfbp1）被选为早期检测肝损伤的最佳候选基因，因为它在治疗过程中显示出早期且持续增强的诱导作用。与微阵列数据一致，在ALD临床前期发展过程中，肝脏组织中的Igfbp1mRNA表达和血清IGFBP1蛋白水平均呈渐进性显著增加。

结论

结果表明，结合其他检测方法，血清IGFBPI蛋白可为早期检测人类酒精性肝损伤提供一种易于测量的生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83cf/4016206/5dce10e1d412/1479-5876-11-266-3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83cf/4016206/df73df0b96d4/1479-5876-11-266-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83cf/4016206/9112186f77c1/1479-5876-11-266-2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83cf/4016206/5dce10e1d412/1479-5876-11-266-3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83cf/4016206/df73df0b96d4/1479-5876-11-266-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83cf/4016206/9112186f77c1/1479-5876-11-266-2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83cf/4016206/5dce10e1d412/1479-5876-11-266-3.jpg

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