Application of vascular secretion factor in preparation of biomarker for detecting non-alcoholic steatohepatitis

A steatohepatitis and biomarker technology, applied in the field of biomedicine, can solve the problem of not systematically elucidating the function of liver EC subsets, and achieve the effect of inhibiting induced fibrosis, simple assessment, and inhibiting liver regeneration.

Active Publication Date: 2022-05-24
THE WEST CHINA SECOND UNIV HOSPITAL OF SICHUAN
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the functional contribution of hepatic EC subsets to human cirrhosis or NASH pathology has not been systematically elucidated at the single-cell level in current clinical and preclinical models

Method used

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  • Application of vascular secretion factor in preparation of biomarker for detecting non-alcoholic steatohepatitis
  • Application of vascular secretion factor in preparation of biomarker for detecting non-alcoholic steatohepatitis
  • Application of vascular secretion factor in preparation of biomarker for detecting non-alcoholic steatohepatitis

Examples

Experimental program
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Effect test

Embodiment 1

[0068] Example 1: Materials and Methods

[0069] 1. Patient and clinical samples. Liver and plasma samples of patients were collected at West China Hospital of Sichuan University with informed consent. Healthy liver tissue (without fibrosis) was obtained from patients with hepatic hemangiomas who underwent endoscopic liver resection. Cirrhotic liver tissue was obtained from patients with histologically diagnosed hepatic fibrosis. Patient information used for scRNA-Seq, liquid microarray analysis, and gene expression analysis is shown in Table 1. Plasma samples were obtained from healthy volunteers (n=21), simple fatty liver (n=16), early nonalcoholic steatohepatitis (F0-F1) (n=12), and different pathological grades of cirrhosis / fibrosis Patients (no cancer) (n=75). Fibrosis grade in non-NASH livers was determined by Fibrosis-4 Index (Fib-4) and Transient Elastography (TE) using NAFLD Fibrosis Index (NFS), Fib-4, TE and controlled attenuation parameters ( CAP) to determine...

Embodiment 2

[0111] Example 2: scRNA-Seq reveals vascular dysregulation and abnormal endothelial classification in human cirrhotic liver

[0112] NPCs were isolated from fresh normal and cirrhotic human livers and subjected to scRNA-seq (10x genomics) ( Figure 1A , Table S1). Healthy liver tissue (without fibrosis) was obtained from a patient with hepatic hemangioma in West China Hospital, and cirrhotic liver tissue was obtained from a patient with histologically diagnosed cirrhosis. 22,374 NPCs from 2 healthy livers and 2 cirrhotic livers were clustered into 25 clusters ( Figure 10A -B). Seven cell lines were defined by expression of marker genes: T cells, B cells, endothelial cells (EC), macrophages (Mac), neutrophils (Neu), dendritic cells (DC), and EPCAM + cells and bile duct cells (EPCAM + )( Figure 1B -C). Experimenters of the present invention found that among all the cell types tested, ECs had the most differential genes ( Figure 1D ). The proportion of ECs in cirrhotic l...

Embodiment 3

[0114] Example 3: Epigenetic reprogramming of liver ECs induces pro-fibrotic "sinusoidal endothelial-macrovascular endothelial dysregulation"

[0115] Epigenetic regulation (histone modification and DNA methylation) plays an important role in the progression of liver fibrosis. However, the functional roles of histone modifications and DNA methylation in different cell lines of human cirrhotic / fibrotic NPCs remain unclear. To this end, the experimenters first determined the histone modifications of parenchymal cells and NPCs in healthy livers and cirrhotic livers. Liquid-chip analysis of histone H3 and H4 modifications showed that compared with healthy livers, NPCs in human cirrhotic livers were more Histone acetylation was significantly reduced, whereas parenchymal cells (hepatocytes) were not significantly different ( Figure 1G ), suggesting epigenetic reprogramming of NPCs in human cirrhotic livers.

[0116] The experimenters further investigated epigenetic changes in dif...

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Abstract

The invention belongs to the field of biological medicine, and mainly relates to application of a vascular secretion factor in preparation of a biomarker for detecting non-alcoholic steatohepatitis. The invention provides an application of a vascular secretion factor in preparation of a biomarker for detecting non-alcoholic steatohepatitis, and is characterized in that the vascular secretion factor comprises IGFBP7 and/or ADAMTS1; the IGFBP7 and/or the ADAMTS1 are/is expressed in an HDAC2 (histone deacetylase 2)/DNMT1-IGFBP7/ADAMTS1-Th17 signal channel. The invention also provides application of the vascular secretion factor in preparation of the biomarker for distinguishing the non-alcoholic steatohepatitis and the simple fatty liver, and is characterized in that the vascular secretion factor comprises IGFBP7 and/or ADAMTS1; the IGFBP7 and/or the ADAMTS1 are/is expressed in an HDAC2 (histone deacetylase 2)/DNMT1-IGFBP7/ADAMTS1-Th17 signal channel. The invention further provides application of the synergistic effect of the IGFBP7 and/or the ADAMTS1 in preparation of the biomarker for detecting the non-alcoholic steatohepatitis. According to the application provided by the invention, the non-alcoholic steatohepatitis can be evaluated more reliably, simply, conveniently and noninvasively.

Description

technical field [0001] The invention belongs to the field of biomedicine, and mainly relates to the application of a vascular secretion factor in preparing a biomarker for detecting nonalcoholic steatohepatitis. Background technique [0002] The liver has the regenerative ability to repair itself after injury. However, in nonalcoholic steatohepatitis (NASH), liver regeneration is inhibited. Similar to diabetes and metabolic syndrome, NASH is on the rise globally. NASH can lead to liver fibrosis, cirrhosis and liver failure. Without effective anti-fibrotic treatment, liver fibrosis and liver cirrhosis caused by NASH usually lead to systemic complications and will become a major global health burden. A major obstacle to the clinical development of NASH treatments is the lack of clinical and preclinical studies of cellular and molecular networks that systematically mimic the pathogenesis of NASH. [0003] The liver is composed of parenchymal cells (hepatocytes) and non-paren...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12Q1/6883G01N33/576G01N33/573G01N33/68
CPCA61K45/06A61K31/506A61K31/706A61P1/16A61P3/10A61P3/06A61K2300/00
Inventor 丁楅森曹中炜张华马永源
Owner THE WEST CHINA SECOND UNIV HOSPITAL OF SICHUAN
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