Insulin-Like Growth Factor-I, Inflammatory Proteins, and Fibrosis in Subjects With Nonalcoholic Fatty Liver Disease
Insulin-Like Growth Factor-I, Inflammatory Proteins, and Fibrosis in Subjects With Nonalcoholic Fatty Liver Disease
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DOI：
10.1210/jc.2012-3290
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发表时间：
2013-02-01
影响因子：
5.8
通讯作者：
Sesti, Giorgio
中科院分区：
文献类型：
--
作者：
Hribal, Marta Letizia;Procopio, Teresa;Sesti, Giorgio
内容：炎症可能在非酒精性脂肪性肝病（NAFLD）的进展中起致病作用;相反，抗炎分子的作用尚未得到解决。在NAFLD受试者中已经描述了低循环水平的抗炎分子IGF-I。目的：本研究的目的是阐明IGF-I在NAFLD中的临床意义及其与炎症生物标志物和纤维化的关系。设计和设置：我们进行了交叉测试-肝HepG 2细胞的截面研究和体外实验，在内科和胃肠和肝脏单位的大学Catanzaro和巴勒莫。受试者：共有221名经超声诊断的NAFLD患者（队列1）和50名经活检证实的NAFLD患者（队列2）参加了这项研究。干预：对队列1进行肝脏超声检查，并从队列2获得肝活检。用特定测定法评估IGF-I和炎性生物标志物血浆浓度。在体外研究中，实时RT-PCR被用来评估急性期reactors.Results mRNA的表达水平：在第一队列中，循环IGF-I水平与NAFLD纤维化评分和炎症生物标志物呈负相关;同样在第二队列中，肝脏IGF-I mRNA水平与纤维化评分呈负相关。最后，我们发现，IGF-I能够直接调节急性期反应物的表达，降低C-反应蛋白和纤维蛋白原水平，上调白蛋白表达在HepG 2 cells.Conclusions：目前的数据表明，循环IGF-I和促炎标志物的评价可能是有用的，以全面评估疾病的严重程度在个人与NAFLD。（临床内分泌代谢杂志98：E304-E308，2013）
Context: Inflammation may have a pathogenic role in the progression of nonalcoholic fatty liver disease (NAFLD); by contrast, the role of anti-inflammatory molecules has not been addressed. Low circulating levels of the anti-inflammatory molecule IGF-I have been described in subjects with NAFLD.Objective: The aim of the study was to elucidate the clinical significance of IGF-I in NAFLD and its relationship with inflammatory biomarkers and fibrosis.Design and Setting: We conducted a cross-sectional study and in vitro experiments on hepatic HepG2 cells at the Internal Medicine and Gastrointestinal and Liver Units of the Universities of Catanzaro and Palermo.Subjects: A total of 221 individuals with NAFLD diagnosed on ultrasonography (cohort 1) and 50 subjects with biopsy-proven NAFLD (cohort 2) participated in the study.Intervention: Liver ultrasonography was performed on cohort 1, and hepatic biopsies were obtained from cohort 2.Main Outcome Measures: NAFLD fibrosis and Kleiner scores were calculated. IGF-I and inflammatory biomarker plasma concentrations were assessed with specific assays. In the in vitro study, real-time RT-PCR was used to assess the mRNA expression levels of acute-phase reactants.Results: In the first cohort, circulating IGF-I levels showed an inverse correlation with NAFLD fibrosis score and inflammatory biomarkers; similarly in the second cohort, liver IGF-I mRNA levels and the fibrosis score showed a negative relationship. Finally, we showed that IGF-I was able to directly modulate the expression of acute-phase reactants, decreasing C-reactive protein and fibrinogen levels and up-regulating albumin expression in HepG2 cells.Conclusions: The present data suggest that evaluation of circulating IGF-I and proinflammatory markers might be useful to assess comprehensively the severity of the disease in individuals with NAFLD. (J Clin Endocrinol Metab 98: E304-E308, 2013)