CN-122012691-A - Application of S100A11 as diagnostic marker and therapeutic target of acute liver injury caused by acetaminophen

Abstract

The invention discloses an application of S100A11 as a diagnostic marker and a therapeutic target of acute liver injury caused by acetaminophen, belonging to the technical field of biological medicine. Aiming at the problem that acute liver injury caused by acetaminophen (APAP) lacks specific diagnostic markers and therapeutic targets, the invention discovers and proves that S100A11 is specifically and highly expressed in the APAP liver injury for the first time. Based on the above, the invention provides the application of S100A11 as a biomarker in preparing an APAP liver injury diagnosis product and the application of S100A11 as a therapeutic target in preparing a medicament for preventing and/or treating APAP liver injury. Specifically, inhibiting the expression or activity of S100a11 (e.g., by siRNA, antibodies, or small molecule compounds) is effective in alleviating acute liver injury caused by APAP. The invention provides a brand new scheme for noninvasive early diagnosis and targeted treatment of APAP liver injury, and has important clinical application value.

Inventors

• ZOU XIAOJU
• SHI CAN
• WU HUIYIN
• LIANG BIN
• Wu Xianxiong
• YU CONGTAO

Assignees

• 云南中医药大学

Dates

Publication Date

20260512

Application Date

20260130

Claims (7)

1. 1. Use of an S100a11 gene or protein for the preparation of a product for diagnosing acute liver injury caused by acetaminophen.
2. 2. The use according to claim 1, wherein the product comprises a reagent or kit for detecting the expression level of the S100a11 gene.
3. 3. The use according to claim 2, wherein the reagent or kit comprises primers or probes for detecting S100a11 mRNA.
4. 4. The use according to claim 2, wherein the reagent or kit comprises an antibody for detecting the S100a11 protein.
5. Application of S100A11 gene or protein as target in preparing medicine for preventing and/or treating acute liver injury caused by acetaminophen.
6. Use of an inhibitor of s100a11 in the manufacture of a medicament for the prevention and/or treatment of acute liver injury caused by acetaminophen.
7. 7. The application of S100A11 gene or protein in screening medicines for treating acute liver injury caused by acetaminophen.

Description

Application of S100A11 as diagnostic marker and therapeutic target of acute liver injury caused by acetaminophen Technical Field The invention belongs to the technical field of biological medicines, and particularly relates to application of an S100A11 gene or protein as a diagnostic marker and a therapeutic target of acute liver injury caused by acetaminophen. Background Acetaminophen (Acetaminophen, APAP) is a widely used antipyretic analgesic, but its excessive use is one of the main causes of acute liver failure. Currently, clinical diagnosis of Drug Induced Liver Injury (DILI), especially APAP liver injury, mainly relies on detection and medical history assessment of serum biochemical indicators (such as alanine aminotransferase ALT, aspartate aminotransferase AST), and the gold standard of diagnosis is liver biopsy. However, liver biopsies are invasive, may cause complications, and are not suitable for dynamic monitoring. Therefore, the novel noninvasive biomarker with high specificity and good sensitivity is searched, and has important significance for early diagnosis, disease assessment and prognosis judgment of APAP liver injury. In terms of treatment, the current main means of clinical treatment of APAP poisoning is the early use of N-acetylcysteine (NAC), but its treatment time window is narrow and has limited effect on some patients. Therefore, the development of therapeutic targets and drugs for new mechanisms of APAP liver injury is a current clinical problem to be solved urgently. S100a11 is a member of the S100 calbindin family, involved in a variety of pathophysiological processes. The effect of the polypeptide in acute liver injury caused by APAP has not been reported, and the polypeptide is not proposed to be used as a biological diagnosis marker or a therapeutic intervention target of the disease. Disclosure of Invention Aiming at the problems in the prior art, the invention aims to provide a novel application of the S100A11 gene or protein as a diagnostic marker and a therapeutic target of acute liver injury caused by acetaminophen. In a first aspect, the invention provides the use of the S100a11 gene or protein in the manufacture of a product for diagnosing acute liver injury caused by acetaminophen. The product comprises a reagent or a kit for detecting the expression level of the S100A11 gene. Preferably, the reagent or kit comprises a primer or probe for detecting S100a11 mRNA, or an antibody for detecting S100a11 protein. In a second aspect, the invention provides an application of S100A11 gene or protein as a target in preparing a medicament for preventing and/or treating acute liver injury caused by acetaminophen. In a third aspect, the present invention provides the use of an S100a11 inhibitor for the manufacture of a medicament for the prevention and/or treatment of acute liver injury caused by acetaminophen. Preferably, the S100a11 inhibitor is selected from: siRNA, antibody or small molecule compound that specifically inhibits S100a11 expression or activity. The medicament can significantly reduce serum alanine Aminotransferase (ALT) and/or aspartate Aminotransferase (AST) levels in a acetaminophen-induced liver injury model, and reduce liver histopathological injury, including reducing hepatocyte necrosis and inflammatory cell infiltration. In a fourth aspect, the invention provides application of S100A11 gene or protein in screening medicines for treating acute liver injury caused by acetaminophen. Compared with the prior art, the invention has the following remarkable advantages: The invention firstly reveals that the S100A11 is obviously up-regulated in a cell model and an animal model of APAP liver injury, the expression level of the S100A11 is positively correlated with the injury degree, and the S100A11 has the potential of becoming an ideal diagnostic marker. Through experiments of specifically knocking out the S100A11 by the liver, the inhibition of the S100A11 can obviously reduce the serum ALT/AST level, lighten pathological damage of liver tissues and clearly determine the effectiveness of the inhibitor as a treatment target. The diagnosis product based on S100A11 can realize noninvasive, early and specific diagnosis, and the treatment strategy (such as gene silencing, antibody or small molecule inhibitor) based on the target spot provides a clear direction for developing novel therapeutic drugs for APAP liver injury. The construction of the S100A11 knockout and overexpression cell model can provide an effective tool for further researching the action mechanism of the S100A11 in the hepatic injury caused by APAP, screening drugs for improving and treating the hepatic injury caused by APAP on a large scale, evaluating whether the drugs have potential hepatic injury risks or not, and the like. Drawings FIG. 1 shows experimental results of a paracetamol induced cell injury model, wherein A is a schematic diagram of a construction flow of the paracetamol cell injury m