CN-122005751-A - Application of Pingpin PDPN in preparation of medicaments for treating viral myocarditis

Abstract

The invention belongs to the technical field of biology, and particularly relates to application of flat foot protein (Podoplanin, PDPN) in preparation of a medicament for treating viral myocarditis. More specifically, the invention provides a novel immunogenic peptide PDPN-TE12 aiming at PDPN, a coding sequence thereof, a pharmaceutical composition containing the peptide and application thereof in preventing and/or treating inflammatory cardiomyopathy such as viral myocarditis and the like. Experimental results show that the polypeptide PDPN-TE12 can obviously relieve myocardial injury of mice with viral myocarditis and inhibit inflammatory cell infiltration and inflammatory cytokine expression, so that the polypeptide PDPN-TE12 can be used as a potential medicament for treating viral myocarditis and provides a new candidate strategy for accurate targeted treatment of the disease.

Inventors

• YUAN JING
• LIU CHANGHU
• YU CHENG

Assignees

• 华中科技大学同济医学院附属协和医院

Dates

Publication Date

20260512

Application Date

20260227

Claims (5)

1. 1. Application of Pinpin protein PDPN in preparing medicine for treating viral myocarditis is provided.
2. 2. An immunogenic peptide directed against ponin PDPN, wherein said immunogenic peptide has an amino acid sequence TQRERGTKPPLE.
3. 3. A pharmaceutical composition comprising a therapeutically effective amount of the immunogenic polypeptide of claim 2 and a pharmaceutically acceptable carrier or excipient.
4. 4. Use of the immunogenic polypeptide of claim 2 or the pharmaceutical composition of claim 3 in the manufacture of a medicament for the prevention or treatment of viral myocarditis.
5. 5. The use according to claim 4, wherein said viral myocarditis is caused by infection with coxsackievirus B3, said coxsackievirus B3 being abbreviated as CVB3.

Description

Application of Pingpin PDPN in preparation of medicaments for treating viral myocarditis Technical Field The invention belongs to the field of biological medicine, and in particular relates to an immunomodulatory polypeptide and application thereof. More particularly, the present invention relates to an immunogenic peptide fragment derived from mouse copeptin (Podoplanin, PDPN), its coding sequence, pharmaceutical compositions comprising the peptide fragment, and its use in the preparation of a medicament for the prevention and/or treatment of viral myocarditis. Background Viral Myocarditis (VMC) is a myocardial inflammatory disease caused by a cardiophilic viral infection (e.g., coxsackievirus B3, influenza virus, etc.). The disease has various clinical manifestations, the light patients can self-heal, but the severe patients can be complicated with heart failure, sudden cardiac death or progress to Dilated Cardiomyopathy (DCM), and the prognosis is poor, thus bringing heavy disease burden to the patients and society. Because of the complex pathogenesis of VMC, the existing treatment mainly supports and symptomatic treatment, and the clinic lacks accurate treatment targets and specific medicines aiming at the key links of diseases at present, so that a new targeting treatment strategy is urgently needed to be developed. The flat foot protein (Podoplanin, PDPN) is a conserved mucin type I transmembrane glycoprotein, is specifically expressed on lymphatic endothelial cells, is widely expressed on various tumor cells and tumor-related fibroblasts, and has close relation with the occurrence, development, invasion and metastasis of various malignant tumors. The platelet aggregation stimulating domain (PLAG) of the extracellular section is selectively combined with C-type lectin (CLEC 2) on platelets to induce the activation and aggregation of the platelets, assist the implantation, adhesion and immune escape of tumor cells, and the polypeptide developed according to the PLAG region of the extracellular section of PDPN can effectively inhibit the invasion and metastasis of malignant tumors. The flat foot protein antagonistic polypeptide disclosed in the patent with publication number CN113461783A can be specifically combined with PDPN to prevent the growth and proliferation of melanoma, and the patent with publication number CN105754953A discloses a monoclonal antibody for resisting human flat foot protein platelet aggregation region and the therapeutic application thereof in lung tumor. However, PDPN has been newly found in recent years to play a key role in the regulation of immune inflammatory cells in cardiovascular disease. 2019. Year Cimini et al found that increased expression of PDPN in the myocardium of Acute Myocardial Infarction (AMI) mice, commercialized monoclonal antibodies can inhibit PDPN expression, significantly improve post-myocardial infarction cardiac function and myocardial remodeling, and along with recruitment and in situ differentiation of anti-inflammatory mononuclear-macrophages (CD 163/CD 206), suggest that PDPN participates in important regulation of ventricular remodeling after myocardial infarction by the mononuclear-macrophage system. Subsequently, in 2021 the present research team found that VMC mice had a large number of Ectopic Lymphoid Follicles (ELFs) formed with germinal centers, which promoted expression of anti-myocardial antibodies (AHA) in myocardial tissue and mediated myocardial injury, and that the mechanism therein was the synergistic interaction of PDPN and IL-17A together mediating ELFs formation, AHA secretion and pathogenic Th17 cell differentiation. Furthermore, the present team further discovered in 2023 that there is a soluble form of PDPN expression in VMC patients, and that its expression is significantly higher than in healthy people and AMI patients, and that it can be used as a novel biomarker for VMC diagnosis and inflammation level prediction, but its specific soluble fragment form is currently unknown. Notably, in VMC studies, we found that the PDPN in vivo regulatory ligand was not the dominant one for CLEC2, and that the CCL21-CCR7 axis expression in the myocardium of VMC mice was significantly inhibited using commercial PDPN antibodies, and furthermore, PDPN in VMC patients was significantly positively correlated with elevated CCL21, while CLEC2 expression was not significantly different in VMC patients. Since the published researches and documents focus mainly on the immune regulation after the PLAG region of PDPN and ligand CLEC2 are activated, SZ168 monoclonal antibodies designed according to the 31-51 amino acid sequence in the PLAG region of the extracellular section of PDPN can directly inhibit PDPN-CLEC2 binding and play the roles of tumor inhibition and platelet activation, in addition, SZ168 is reported to remarkably improve the nerve inflammatory reaction after acute lung injury and cerebral hemorrhage in sepsis, and the PLAG region of the