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Application of Optineurin in preparation of medicine for diagnosing and treating liver cirrhosis

A drug and reverse primer technology, applied in application, drug combination, botanical equipment and methods, etc., can solve the problems of lack of hepatic stellate cells and liver cirrhosis, and achieve the effect of increasing treatment options

Pending Publication Date: 2022-07-26
ZHEJIANG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Existing studies have pointed out that OPTN is low-expressed in tumor tissues of patients with liver cancer, but so far there is no report on its effect on hepatic stellate cells and liver cirrhosis

Method used

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  • Application of Optineurin in preparation of medicine for diagnosing and treating liver cirrhosis
  • Application of Optineurin in preparation of medicine for diagnosing and treating liver cirrhosis
  • Application of Optineurin in preparation of medicine for diagnosing and treating liver cirrhosis

Examples

Experimental program
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Effect test

Embodiment 1

[0030] The GSE 25097 dataset was analyzed using the GEO database to compare the mRNA levels of OPTN in cirrhotic patients and normal individuals, as shown in figure 1 The results of A showed that the expression of OPTN was significantly up-regulated in the liver tissue of patients with liver cirrhosis, and was positively correlated with the collagen-related gene COL1A1 and the hepatic stellate cell activation marker gene ACTA2. The paraffin section samples of liver tissue from patients with liver cirrhosis were used to detect the expression of OPTN protein by OPTN antibody drug after dewaxing. 0.1% sodium azide and 0.1% gelatin. like figure 1As shown in B, compared with healthy patients, the expression of OPTN protein in patients with liver cirrhosis significantly increased, and the expression of OPTN protein was positively correlated with the disease process of patients with liver cirrhosis, which was consistent with the H&E staining results in the prior art, indicating that...

Embodiment 2

[0032] The GSE 55747 dataset was analyzed using the GEO database to compare the mRNA levels of OPTN in cirrhotic and normal mice, as shown in figure 2 The results of A showed that the expression of OPTN was significantly up-regulated in cirrhotic liver tissue. WT mice were taken, and bile duct ligation was performed to construct an animal model of cholestatic liver cirrhosis; or 25% carbon tetrachloride (CCl 4 ) to construct an animal model of poison-induced liver cirrhosis. Tissue samples were collected, embedded in paraffin and sectioned, and the expression of OPTN protein was detected by OPTN antibody drug. like figure 2 The results of B showed that compared with the normal control group, OPTN protein significantly increased the fibrotic deposition area in the liver tissue of animal models of cholestatic and poison-induced liver cirrhosis, suggesting that OPTN antibody drugs have good effects in mouse liver cirrhosis. diagnostic effect.

Embodiment 3

[0034] Take wild type (WT) and OPTN knockout (Optn - / - ) mice constructed with bile duct ligation or CCl 4 In the animal model of induced liver cirrhosis, liver samples were collected for paraffin section and then H&E staining and Sirius red staining were performed to investigate the pathological symptoms of the two mice. like image 3 The results showed that hepatic hepatocyte necrosis and collagen fiber formation in OPTN-null mice were significantly less than those in wild-type mice ( image 3 A). Extraction of protein and RNA from liver samples, OPTN deletion significantly reduced collagen COL1A1 and α-SMA expression ( image 3 B), OPTN deletion significantly suppressed the mRNA levels of fibrosis-related genes Acta2, Col1a1, Timp1, Tgfb ( image 3 C). These results indicate that OPTN protein deletion can significantly alleviate liver cirrhosis symptoms, including hepatocyte necrosis and fibrosis, suggesting that inhibiting OPTN protein expression is an effective strat...

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Abstract

The invention provides an application of Optineurin in preparation of a medicine for diagnosing and treating liver cirrhosis. OPTN comprises an antibody for targeting an OPTN protein, a primer for targeting an OPTN gene and interference siRNAs (small interfering ribonucleic acids). The invention proves that mRNA and protein levels of OPTN increase in liver cirrhosis liver tissues, and the antibody specifically targeting OPTN protein can effectively diagnose liver cirrhosis; oPTN protein deletion can significantly relieve liver fibrosis symptoms of mice with liver cirrhosis; when the interference siRNAs of the targeted OPTN gene are applied to the hepatic stellate cells, a TGF-beta signal channel and induced hepatic stellate cell activation and collagen secretion can be inhibited. The invention can be used for preparing medicines for diagnosing and predicting cirrhosis, or can be used as a specific marker for diagnosing cirrhosis, so that the clinical diagnosis of cirrhosis is more accurate and quicker; the siRNAs targeting the OPTN gene and the like can be used as effective medicines for treating liver cirrhosis.

Description

technical field [0001] The invention belongs to the field of biopharmaceuticals, and relates to the application of Optineurin in preparing medicines for diagnosis and treatment of liver cirrhosis. Background technique [0002] Liver cirrhosis is a progressive liver injury caused by the long-term action of various pathogenic factors leading to excessive deposition of extracellular matrix (ECM) to form fibrils, accompanied by complications such as ascites, sepsis, hepatic encephalopathy, and hepatorenal syndrome. Treatment can lead to multiple organ failure and even liver cancer, which eventually leads to the death of the patient. The activation of Hepatic Stellate Cells (HSCs) is the key reason for excessive deposition of ECM to cause liver cirrhosis: HSCs are induced and activated by a variety of stimulatory factors, and the activated HSCs synthesize and secrete a large amount of collagen, resulting in excessive deposition of ECM to form fibers, cause liver cirrhosis. In m...

Claims

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Application Information

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IPC IPC(8): C07K14/47C07K16/18C12N15/12C12Q1/6883C12N15/11C12N15/113A61K39/395A61K31/713A61K45/00A61P1/16
CPCC07K14/47C07K16/18C12Q1/6883C12N15/113A61K31/713A61K45/00A61P1/16A61K2039/505C12N2310/141C12Q2600/106
Inventor 何俏军蔡萱妍杨波王佳佳翁勤洁
Owner ZHEJIANG UNIV
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