Research Unit of Multifactorial Genetics and Epigenetics, "Bambino Gesù" Children's Hospital-IRCCS, Rome, Italy.
NORDFERTIL Research Lab Stockholm, Paediatric Endocrinology Unit, Department of Women's and Children's Health, Karolinska Institutet and University Hospital, Solna, Sweden.
PLoS One. 2018 Jul 31;13(7):e0201566. doi: 10.1371/journal.pone.0201566. eCollection 2018.
Nonalcoholic fatty liver disease is one of the major complications of obesity, occurring already in pediatric age. Insulin like growth factor-I has been proposed as a potential therapeutic agent for its beneficial effect in experimental liver fibrosis. The aim of this work was to investigate the expression of insulin-like growth factor-I and its receptor in the liver of children with biopsy-proven nonalcoholic fatty liver disease and relate it to liver histological features.
45 obese children and adolescents (14 females and 31 males) with nonalcoholic fatty liver disease were included. Insulin like growth factor-I and its receptor expression was evaluated in liver tissue by immunofluorescence and qPCR.
The expression of insulin like growth factor-I and its receptor were significantly related to fibrosis and were higher in children with stage 3 fibrosis compared to stage 1 and 2 (p<0.001 and p = 0.007 respectively). mRNA of insulin like growth factor-I receptor was higher in more advanced stages of fibrosis (p<0.001). Furthermore, the expression of insulin like growth factor-I and its receptor in hepatic stellate cells, the cell type mostly involved in fibrosis progression, was significantly increased in stage 3 fibrosis compared to stage 1 (p = 0.01 and p = 0.008 respectively).
We demonstrated for the first time that insulin like growth factor-I and its receptor are upregulated in children with nonalcoholic fatty liver disease. These findings give a new hint for the potential therapeutic use of insulin like growth factor-I in pediatric nonalcoholic fatty liver disease complicated by liver fibrosis.
非酒精性脂肪性肝病是肥胖症的主要并发症之一，在儿科时期就已发生。胰岛素样生长因子-I 因其在实验性肝纤维化中的有益作用而被提议作为一种潜在的治疗药物。本研究旨在研究经活检证实的非酒精性脂肪性肝病患儿肝脏中胰岛素样生长因子-I 及其受体的表达，并将其与肝脏组织学特征相关联。
纳入 45 名经活检证实患有非酒精性脂肪性肝病的肥胖儿童和青少年（14 名女性和 31 名男性）。通过免疫荧光和 qPCR 评估肝脏组织中胰岛素样生长因子-I 和其受体的表达。
胰岛素样生长因子-I 和其受体的表达与纤维化显著相关，且在 3 期纤维化患儿中明显高于 1 期和 2 期（p<0.001 和 p = 0.007）。胰岛素样生长因子-I 受体的 mRNA 在纤维化程度较高的阶段更高（p<0.001）。此外，在纤维化程度较高的 3 期，肝星状细胞中胰岛素样生长因子-I 和其受体的表达明显高于 1 期（p = 0.01 和 p = 0.008）。
我们首次证明，胰岛素样生长因子-I 和其受体在非酒精性脂肪性肝病患儿中上调。这些发现为胰岛素样生长因子-I 在伴有肝纤维化的小儿非酒精性脂肪性肝病中的潜在治疗用途提供了新的线索。
