Distinct Hepatic Gene-Expression Patterns of NAFLD in Patients With Obesity.
Distinct Hepatic Gene-Expression Patterns of NAFLD in Patients With Obesity.
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DOI：
10.1002/hep4.1789
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发表时间：
2022-01
影响因子：
5.1
通讯作者：
Corey KE
中科院分区：
文献类型：
--
作者：
Subudhi S;Drescher HK;Dichtel LE;Bartsch LM;Chung RT;Hutter MM;Gee DW;Meireles OR;Witkowski ER;Gelrud L;Masia R;Osganian SA;Gustafson JL;Rwema S;Bredella MA;Bhatia SN;Warren A;Miller KK;Lauer GM;Corey KE
由于对疾病发病机制的不完全了解，治疗非酒精性脂肪肝 (NAFLD) 的方法受到限制。本研究的目的是确定肥胖成人高危人群中与不同肝损伤模式相关的肝脏基因表达模式。使用 NanoString Technologies（华盛顿州西雅图）的 nCounter 测定，我们对 318 名肥胖成人的肝组织中 795 个基因的表达进行了定量，这些基因被假设与肝纤维化、炎症和脂肪变性有关。肝脏标本被分为四种不同的 NAFLD 表型：正常肝脏组织学 (NLH)、仅脂肪变性 (脂肪变性)、无纤维化的非酒精性脂肪性肝炎 (NASH F0) 和 1-4 期纤维化 NASH (NASH F1-F4)。随着 NAFLD 病理的进展，一百二十五个基因显着增加或减少。与NLH相比，NASH F0的特点是炎症基因表达增加，例如γ-干扰素诱导的溶酶体硫醇还原酶（IFI30）和趋化因子（C-X-C基序）配体9（CXCL9），而补体和凝血相关基因，例如C9和补体成分4结合蛋白β（C4BPB）减少。在 NASH F1-F4 存在的情况下，细胞外基质降解蛋白酶和促纤维化/疤痕沉积基因，如胶原蛋白和转化生长因子 β 1 (TGFB1) 同时增加，表明组织重塑处于动态状态。结论：在肥胖成人中，NAFLD 的不同状态与肝内炎症、补体和凝血途径以及组织重塑相关基因的扰动有关。这些数据为高危个体中 NAFLD 的动态发病机制提供了见解。
Approaches to manage nonalcoholic fatty liver disease (NAFLD) are limited by an incomplete understanding of disease pathogenesis. The aim of this study was to identify hepatic gene‐expression patterns associated with different patterns of liver injury in a high‐risk cohort of adults with obesity. Using the NanoString Technologies (Seattle, WA) nCounter assay, we quantified expression of 795 genes, hypothesized to be involved in hepatic fibrosis, inflammation, and steatosis, in liver tissue from 318 adults with obesity. Liver specimens were categorized into four distinct NAFLD phenotypes: normal liver histology (NLH), steatosis only (steatosis), nonalcoholic steatohepatitis without fibrosis (NASH F0), and NASH with fibrosis stage 1‐4 (NASH F1‐F4). One hundred twenty‐five genes were significantly increasing or decreasing as NAFLD pathology progressed. Compared with NLH, NASH F0 was characterized by increased inflammatory gene expression, such as gamma‐interferon‐inducible lysosomal thiol reductase (IFI30) and chemokine (C‐X‐C motif) ligand 9 (CXCL9), while complement and coagulation related genes, such as C9 and complement component 4 binding protein beta (C4BPB), were reduced. In the presence of NASH F1‐F4, extracellular matrix degrading proteinases and profibrotic/scar deposition genes, such as collagens and transforming growth factor beta 1 (TGFB1), were simultaneously increased, suggesting a dynamic state of tissue remodeling. Conclusion: In adults with obesity, distinct states of NAFLD are associated with intrahepatic perturbations in genes related to inflammation, complement and coagulation pathways, and tissue remodeling. These data provide insights into the dynamic pathogenesis of NAFLD in high‐risk individuals.
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影响因子：
14.9
作者：
Ritchie ME;Phipson B;Wu D;Hu Y;Law CW;Shi W;Smyth GK
通讯作者：
Smyth GK
影响因子：
5.2
作者：
Seda, Ondrej;Cahova, Monika;Trunecka, Pavel
通讯作者：
Trunecka, Pavel
影响因子：
13.5
作者：
Rensen, Sander S.;Slaats, Yanti;Buurman, Wim A.
通讯作者：
Buurman, Wim A.
影响因子：
24.5
作者：
Baselli, Guido Alessandro;Dongiovanni, Paola;Valenti, Luca
通讯作者：
Valenti, Luca
影响因子：
2.3
作者：
Bellentani, Stefano;Scaglioni, Federica;Bedogni, Giorgio
通讯作者：
Bedogni, Giorgio