CN115177730B - Ptpn22及其表达抑制剂的新用途 - Google Patents
Ptpn22及其表达抑制剂的新用途 Download PDFInfo
- Publication number
- CN115177730B CN115177730B CN202210936561.7A CN202210936561A CN115177730B CN 115177730 B CN115177730 B CN 115177730B CN 202210936561 A CN202210936561 A CN 202210936561A CN 115177730 B CN115177730 B CN 115177730B
- Authority
- CN
- China
- Prior art keywords
- ptpn22
- heart failure
- expression
- chronic heart
- preparation
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 101001135589 Homo sapiens Tyrosine-protein phosphatase non-receptor type 22 Proteins 0.000 title claims abstract description 67
- 102100033138 Tyrosine-protein phosphatase non-receptor type 22 Human genes 0.000 title claims abstract description 67
- 239000003112 inhibitor Substances 0.000 title abstract description 14
- 206010007558 Cardiac failure chronic Diseases 0.000 claims abstract description 41
- 210000001744 T-lymphocyte Anatomy 0.000 claims abstract description 22
- 210000005259 peripheral blood Anatomy 0.000 claims abstract description 14
- 239000011886 peripheral blood Substances 0.000 claims abstract description 14
- 238000001514 detection method Methods 0.000 claims abstract description 9
- 230000002596 correlated effect Effects 0.000 claims description 9
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 238000002965 ELISA Methods 0.000 claims description 2
- 239000003153 chemical reaction reagent Substances 0.000 claims description 2
- 238000009472 formulation Methods 0.000 claims 1
- 239000000203 mixture Substances 0.000 claims 1
- 206010019280 Heart failures Diseases 0.000 abstract description 37
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 16
- 238000002360 preparation method Methods 0.000 abstract description 15
- 108010031988 Non-Receptor Type 22 Protein Tyrosine Phosphatase Proteins 0.000 abstract description 7
- 102000005503 Non-Receptor Type 22 Protein Tyrosine Phosphatase Human genes 0.000 abstract description 7
- 230000030609 dephosphorylation Effects 0.000 abstract description 6
- 238000006209 dephosphorylation reaction Methods 0.000 abstract description 6
- 238000003745 diagnosis Methods 0.000 abstract description 5
- 201000010099 disease Diseases 0.000 abstract description 5
- 239000003814 drug Substances 0.000 abstract description 4
- 238000012216 screening Methods 0.000 abstract description 4
- 238000004393 prognosis Methods 0.000 abstract description 3
- 230000000302 ischemic effect Effects 0.000 description 18
- 230000026731 phosphorylation Effects 0.000 description 14
- 238000006366 phosphorylation reaction Methods 0.000 description 14
- 102100036011 T-cell surface glycoprotein CD4 Human genes 0.000 description 9
- 210000003289 regulatory T cell Anatomy 0.000 description 8
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 7
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 7
- 230000002861 ventricular Effects 0.000 description 7
- 230000004913 activation Effects 0.000 description 5
- 230000004069 differentiation Effects 0.000 description 5
- 101800000407 Brain natriuretic peptide 32 Proteins 0.000 description 4
- 230000000875 corresponding effect Effects 0.000 description 4
- 230000011664 signaling Effects 0.000 description 4
- 108020004459 Small interfering RNA Proteins 0.000 description 3
- 238000000684 flow cytometry Methods 0.000 description 3
- 239000000758 substrate Substances 0.000 description 3
- 238000010220 Pearson correlation analysis Methods 0.000 description 2
- 102000001253 Protein Kinase Human genes 0.000 description 2
- 102000007624 ZAP-70 Protein-Tyrosine Kinase Human genes 0.000 description 2
- 108010046882 ZAP-70 Protein-Tyrosine Kinase Proteins 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 230000002107 myocardial effect Effects 0.000 description 2
- 108060006633 protein kinase Proteins 0.000 description 2
- 230000009467 reduction Effects 0.000 description 2
- 230000001105 regulatory effect Effects 0.000 description 2
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- 101800002247 Brain natriuretic peptide 45 Proteins 0.000 description 1
- 206010007556 Cardiac failure acute Diseases 0.000 description 1
- 206010016654 Fibrosis Diseases 0.000 description 1
- 101000914514 Homo sapiens T-cell-specific surface glycoprotein CD28 Proteins 0.000 description 1
- 241000713666 Lentivirus Species 0.000 description 1
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 1
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 1
- 229940100514 Syk tyrosine kinase inhibitor Drugs 0.000 description 1
- 230000006044 T cell activation Effects 0.000 description 1
- 102100027213 T-cell-specific surface glycoprotein CD28 Human genes 0.000 description 1
- 208000033774 Ventricular Remodeling Diseases 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000008827 biological function Effects 0.000 description 1
- 230000001164 bioregulatory effect Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 230000009787 cardiac fibrosis Effects 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 230000024245 cell differentiation Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 230000012085 chronic inflammatory response Effects 0.000 description 1
- 230000009091 contractile dysfunction Effects 0.000 description 1
- 238000010219 correlation analysis Methods 0.000 description 1
- 238000013480 data collection Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- -1 etc. Proteins 0.000 description 1
- 230000004761 fibrosis Effects 0.000 description 1
- 230000004217 heart function Effects 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 210000004698 lymphocyte Anatomy 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000008506 pathogenesis Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 210000003819 peripheral blood mononuclear cell Anatomy 0.000 description 1
- DCWXELXMIBXGTH-QMMMGPOBSA-N phosphonotyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(OP(O)(O)=O)C=C1 DCWXELXMIBXGTH-QMMMGPOBSA-N 0.000 description 1
- 238000010837 poor prognosis Methods 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000001890 transfection Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/7088—Compounds having three or more nucleosides or nucleotides
- A61K31/713—Double-stranded nucleic acids or oligonucleotides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
- C12Q1/6883—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/573—Immunoassay; Biospecific binding assay; Materials therefor for enzymes or isoenzymes
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q2600/00—Oligonucleotides characterized by their use
- C12Q2600/158—Expression markers
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2333/00—Assays involving biological materials from specific organisms or of a specific nature
- G01N2333/90—Enzymes; Proenzymes
- G01N2333/914—Hydrolases (3)
- G01N2333/916—Hydrolases (3) acting on ester bonds (3.1), e.g. phosphatases (3.1.3), phospholipases C or phospholipases D (3.1.4)
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/32—Cardiovascular disorders
- G01N2800/325—Heart failure or cardiac arrest, e.g. cardiomyopathy, congestive heart failure
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Immunology (AREA)
- Organic Chemistry (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Analytical Chemistry (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Zoology (AREA)
- Microbiology (AREA)
- Urology & Nephrology (AREA)
- Epidemiology (AREA)
- Genetics & Genomics (AREA)
- Pathology (AREA)
- Hematology (AREA)
- Biomedical Technology (AREA)
- Physics & Mathematics (AREA)
- Cardiology (AREA)
- Biotechnology (AREA)
- Wood Science & Technology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Hospice & Palliative Care (AREA)
- Biophysics (AREA)
- General Engineering & Computer Science (AREA)
- Heart & Thoracic Surgery (AREA)
- Cell Biology (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Food Science & Technology (AREA)
- General Physics & Mathematics (AREA)
- Investigating Or Analysing Biological Materials (AREA)
Abstract
本发明属于生物技术领域，具体公开PTPN22及其表达抑制剂的新用途。PTPN22表达抑制剂在制备治疗心力衰竭疾病竭药物中的应用。检测PTPN22表达的制剂在制备筛查诊断心力衰竭疾病产品中的应用。PTPN22表达抑制剂在制备治疗ZAP‑70Y292去磷酸化诱发疾病中的应用。本发明发现了PTPN22在慢性心力衰竭患者外周血CD4+T细胞中升高，通过对PTPN22蛋白表达情况的检测可以用于慢性心力衰竭患者的辅助诊断；PTPN22蛋白可应用于慢性心力衰竭检测试剂盒，进一步丰富慢性心力衰竭诊断及预后检测的位点。
Description
技术领域
本发明属于生物技术领域，尤其涉及PTPN22及其表达抑制剂的新用途。
背景技术
心力衰竭是指心脏失去与代谢组织匹配的泵血能力的病理状态，以间质纤维化、心室顺应性降低以及心室扩张为主要特征。在慢性心力衰竭中，持续的慢性炎症反应对机体的异常调节，会导致左室收缩功能异常、心室重塑以及心脏纤维化。心力衰竭包括急性心力衰竭和慢性心力衰竭，慢性心力衰竭中又有非缺血性心力衰竭和缺血性心力衰竭等不同类型病症。
既往研究探索了蛋白酪氨酸磷酸酶非受体型22(Protein tyrosinephosphatase,nonreceptor type,22，PTPN22)在T细胞激活和自身免疫性疾病中的作用。PTPN22的作用底物包括Zeta链相关蛋白激酶70kDa(Zeta-chain–associated proteinkinase of 70kDa，ZAP-70)、淋巴细胞特异性酪氨酸蛋白激酶等多个磷酸化位点，PTPN22对其底物进行去磷酸化，导致底物磷酸化减少。ZAP-70磷酸化后可以结合至TCR-CD3ζ，参与TCR信号的激活。TCR早期信号的激活可以促进CD4+T细胞向调节性T细胞(Tregs) 转化。然而，过高的TCR信号激活会导致Tregs的分化减少。Tregs的减少已被证明与慢性心力衰竭的不良预后相关。
发明内容
针对上述问题，本发明提供PTPN22及其表达抑制剂的新用途，主要为了研究PTPN22新用途，主要为了探索PTPN22在心力衰竭疾病的诊断、治疗中的应用前景。
为了解决上述问题，本发明采用如下技术方案：
PTPN22表达抑制剂在制备治疗心力衰竭疾病竭药物中的应用。
在一些方式中，所述PTPN22表达抑制剂包括siRNA。
在一些方式中，所述心力衰竭疾病为慢性心力衰竭。
在一些方式中，所述慢性心力衰竭包括非缺血性心力衰竭。
检测PTPN22表达的制剂在制备筛查诊断心力衰竭疾病产品中的应用。
在一些方式中，所述心力衰竭疾病为慢性心力衰竭。
在一些方式中，所述慢性心力衰竭包括非缺血性心力衰竭。
PTPN22表达抑制剂在制备治疗ZAP-70Y292去磷酸化诱发疾病中的应用。
PTPN22在制备ZAP-70Y292去磷酸化产品中非诊断治疗的应用。
本发明的有益效果是：
发现了PTPN22在慢性心力衰竭患者外周血CD4+T细胞中升高，通过对 PTPN22蛋白表达情况的检测可以用于慢性心力衰竭患者的辅助诊断；为慢性心力衰竭的发病机理提供重要线索，对慢性心力衰竭的免疫诊断和治疗具有重要意义；PTPN22蛋白可应用于慢性心力衰竭检测试剂盒，进一步丰富慢性心力衰竭诊断及预后检测的位点。
附图说明
图1：研究人群基本临床特征表；
图2：CHF患者CD4+T细胞中PTPN22表达明显升高；
图3：CHF患者外周血CD4+T细胞PTPN22表达与临床指标的相关性；
图4：siRNA-PTPN22转染CD4+T细胞后，Tregs分化减少；
图5：PTPN22通过去磷酸化ZAP-70Y292调控CD4+T细胞中TCR早期信号。
具体实施方式
下面对本发明做进一步说明：
本部分第一方面介绍PTPN22在制备抗心力衰竭药物中的用途：
PTPN22表达抑制剂在制备治疗心力衰疾病竭药物中的应用。
所述PTPN22表达抑制剂包括siRNA等，其他能够实现抑制或干扰表达的手段均等同。
其中，所述心力衰竭疾病包括慢性心力衰竭，通过抑制PTPN22表达针对慢性心力衰竭具有更好的治疗效果。
慢性心力衰竭主要是慢性原发性心肌病变和心室因长期压力或容量负荷过重，使心肌收缩力减弱，不能维持心排血量。慢性心力衰竭相关衰竭病症中部分属于非缺血性心力衰竭，另有部分属于缺血性心力衰竭。PTPN22表达抑制剂对非缺血性心力衰竭的治疗效果更加明显。
本部分第二方面介绍PTPN22在制备检测产品中的用途：
其中之一，PTPN22在制备筛查心力衰竭产品中的用途：
检测PTPN22表达的制剂在制备筛查诊断心力衰竭疾病产品中的应用。
检测PTPN22表达情况即可得知心力衰竭的严重程度，心力衰竭严重程度提升也会伴随PTPN22表达增加。
其中，所述心力衰竭疾病包括慢性心力衰竭。
更进一步的，所述慢性心力衰竭包括非缺血性心力衰竭和缺血性心力衰竭。其中，PTPN22表达情况与非缺血性心力衰竭的联系更加紧密，通过检测 PTPN22的表达可以更快速准确的检测非缺血性心力衰竭。PTPN22表达情况与缺血性心力衰竭的关联度比非缺血性心力衰竭关联度低。
其中之二，检测PTPN22表达的制剂在制备检测总酪氨酸磷酸化和/或 ZAP-70Y292的磷酸化水平检测产品中的应用。总酪氨酸磷酸化水平与PTPN22 表达水平正相关，ZAP-70Y292的磷酸化与PTPN22表达水平负相关。由此，通过检测所得的PTPN22表达水平即可得知总酪氨酸磷酸化水平、PTPN22表达水平的变化情况。并且，在实验中也整体性的验证了相应的函数关系，尤其是图5中也公开了相应的系数，可以据此进行数值分析，当然为了更准确的进行计算，还需要优化相应的公式。
检测PTPN22表达的制剂包括PCR、ELISA等检测，其中检测PTPN22表达的制剂不局限于一种特定的试剂，凡是能够检测PTPN22表达的产品均在此范围内。
本部分第三方面介绍PTPN22在ZAP-70Y292磷酸化调节产品中的用途：
PTPN22表达抑制剂在制备治疗ZAP-70Y292去磷酸化诱发疾病中的应用。 ZAP-70Y292去磷酸化诱发疾病包括CD4+T细胞分化异常引发的心力衰竭等。
PTPN22在制备ZAP-70Y292去磷酸化产品中非诊断治疗的应用。经过验证可知，PTPN22可以抑制ZAP-70Y292的磷酸化水平。其主要作用于一些非疾病治疗的环境，比如作为一些生物调节制剂。
本部分第四方面结合具体的实验项目作出进一步介绍：
实验准备
样本收集：在收集到40例慢性心力衰竭的患者，11例健康对照。所有参与本发明研究的成员均签署了知情同意书。发明人采集获得上述成员的外周血样本。
临床资料收集：发明人对上述慢性心力衰竭衰竭患者及健康对照的临床基本资料进行了采集，包括年龄、性别、纽约心脏协会(New York Heart Association，NYHA)分级、左心室射血分数(left ventricular ejection fraction，LVEF)、左心室舒张末期容积(leftventricular end-diastolic diameter，LVEDD)、B型钠尿肽(Type B natriureticpeptide，BNP)，如图 1中研究人群基本临床特征表所示。
结果分析
流式检测PTPN22表达：
通过流式细胞术检测上述外周血样本中CD4+T细胞的PTPN22蛋白表达水平。结果显示，相较于健康对照，慢性心力衰竭组外周血CD4+T细胞中PTPN22 明显升高，且两者正相关(图2)。
外周血CD4+T细胞中PTPN22表达与临床指标的关联分析：
采取Pearson’s关联性分析发现，慢性心力衰竭(CHF)患者外周血CD4+T 细胞中PTPN22表达量与血清BNP含量呈正相关(图3中A)，与LVEF呈负相关，与LVEDD呈正相关(图3中B、C)，这些相关性在非缺血性心力衰竭(NIHF) 中更为明显，前述的相关性在缺血性心力衰竭(IHF)中也同样存在。这一结果提示外周血CD4+T细胞中PTPN22表达升高与慢性心力衰竭患者的严重程度及心功能下降明显相关。
减少慢性心力衰竭患者外周血CD4+T细胞中PTPN22表达后Tregs分化增加：
构建了针对PTPN22的小干扰RNA(siRNA),并使用慢病毒进行转染，以降低非缺血性心衰患者外周血CD4+T细胞中PTPN22的表达(图4中A)。随后采用流式细胞术检测CD4+T细胞中Tregs的比例，发现转染siRNA-PTPN22组的Tregs比例增加(图4中B)。说明PTPN22的增加可减少Tregs的分化，从而可能对慢性心力衰竭患者的预后产生影响。
PTPN22通过去磷酸化ZAP-70Y292调控TCR早期信号：
总酪氨酸磷酸化(pTyr)反映TCR早期信号激活强度。ZAP-70 Y319和 ZAP-70 Y292被报道是PTPN22的可能作用位点。在分离慢性心力衰竭患者外周血单个核细胞后，使用CD3/CD28 mAb模拟TCR激活信号，在刺激5分钟时收取细胞，通过流式细胞术检测PTPN22表达和CD4+T细胞的总酪氨酸、ZAP-70 Y319和ZAP-70 Y292的磷酸化水平。如图5中，通过Pearson’s相关性分析发现在慢性心力衰竭组中，PTPN22与总酪氨酸磷酸化呈正相关，与ZAP-70 Y292的磷酸化水平呈负相关，这一趋势在非缺血性和缺血性病因引起的心力衰竭中均保持一致。这一结果提示PTPN22可能通过去磷酸化ZAP-70 Y292这一酪氨酸位点调控慢性心力衰竭患者外周血CD4+T细胞的TCR激活，从而对 CD4+T细胞的分化和生物学功能产生影响。
在上述实验研究的基础上，PTPN22在心力衰竭患者外周血CD4+T细胞中的表达及其应用，主要发现CD4+T细胞中PTPN22升高与心力衰竭患者临床指标的相关性，并填补了慢性心力衰竭的免疫一个方面的漏缺。
本领域的技术人员可以明确，在不脱离本发明的总体精神以及构思的情形下，可以做出对于以上实施例的各种变型。其均落入本发明的保护范围之内。本发明的保护方案以本发明所附的权利要求书为准。
Claims (2)
1.检测PTPN22表达情况的制剂在制备检测慢性心力衰竭严重程度的产品的应用，其中，PTPN22表达水平与慢性心力衰竭严重程度正相关，所述PTPN22源自慢性心力衰竭患者外周血CD4+T细胞。
2.根据权利要求1所述的应用，其中，检测PTPN22表达情况的制剂包括用于PCR、ELISA检测的试剂。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210936561.7A CN115177730B (zh) | 2022-08-05 | 2022-08-05 | Ptpn22及其表达抑制剂的新用途 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210936561.7A CN115177730B (zh) | 2022-08-05 | 2022-08-05 | Ptpn22及其表达抑制剂的新用途 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN115177730A CN115177730A (zh) | 2022-10-14 |
| CN115177730B true CN115177730B (zh) | 2024-02-27 |
Family
ID=83520975
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202210936561.7A Active CN115177730B (zh) | 2022-08-05 | 2022-08-05 | Ptpn22及其表达抑制剂的新用途 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN115177730B (zh) |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2001051509A2 (en) * | 2000-01-10 | 2001-07-19 | The Hospital For Sick Children | Shc-associated protein 140 (sap-140) |
| WO2012072681A1 (en) * | 2010-12-01 | 2012-06-07 | Inserm (Institut National De La Sante Et De La Recherche Medicale) | Diagnostic and treatment of chronic heart failure |
| CN105188767A (zh) * | 2012-07-25 | 2015-12-23 | 布罗德研究所有限公司 | 可诱导的dna结合蛋白和基因组干扰工具及其应用 |
| CN106729757A (zh) * | 2017-03-08 | 2017-05-31 | 复旦大学附属中山医院 | miR‑378抑制心肌肥厚和心肌纤维化并诊断心力衰竭的用途 |
| CN110161242A (zh) * | 2019-05-23 | 2019-08-23 | 华中科技大学同济医学院附属同济医院 | EETs、sEH、sEH抑制剂在慢性心力衰竭中的应用 |
| CN113679736A (zh) * | 2021-09-26 | 2021-11-23 | 华中科技大学同济医学院附属协和医院 | 菊粉新用途 |
-
2022
- 2022-08-05 CN CN202210936561.7A patent/CN115177730B/zh active Active
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2001051509A2 (en) * | 2000-01-10 | 2001-07-19 | The Hospital For Sick Children | Shc-associated protein 140 (sap-140) |
| WO2012072681A1 (en) * | 2010-12-01 | 2012-06-07 | Inserm (Institut National De La Sante Et De La Recherche Medicale) | Diagnostic and treatment of chronic heart failure |
| CN105188767A (zh) * | 2012-07-25 | 2015-12-23 | 布罗德研究所有限公司 | 可诱导的dna结合蛋白和基因组干扰工具及其应用 |
| CN106729757A (zh) * | 2017-03-08 | 2017-05-31 | 复旦大学附属中山医院 | miR‑378抑制心肌肥厚和心肌纤维化并诊断心力衰竭的用途 |
| CN110161242A (zh) * | 2019-05-23 | 2019-08-23 | 华中科技大学同济医学院附属同济医院 | EETs、sEH、sEH抑制剂在慢性心力衰竭中的应用 |
| CN113679736A (zh) * | 2021-09-26 | 2021-11-23 | 华中科技大学同济医学院附属协和医院 | 菊粉新用途 |
Non-Patent Citations (3)
| Title |
|---|
| Intrinsic abnormalities in the signaling machinery of acute coronary syndrome T-cells involving PTPN22 expression and Y-292 Zap70 phosphorylation;D. Flego et al.;European Heart Journal;第34卷;764 * |
| Regulatory T Cells in Chronic Heart Failure;Yuzhi Lu et al.;Frontiers in Immunology;第12卷;1-15 * |
| 慢性心力衰竭患者CD4+CD25+调节性T细胞检测及意义;程翔等;临床心血管病杂志;第22卷;1-3 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN115177730A (zh) | 2022-10-14 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Prins et al. | Interleukin-6 is independently associated with right ventricular function in pulmonary arterial hypertension | |
| US10408845B2 (en) | Methods for treating or predicting risk of a ventricular tachyarrhythmia event | |
| Breidthardt et al. | Heart failure therapy–induced early ST2 changes may offer long-term therapy guidance | |
| Bujak et al. | Aging-related defects are associated with adverse cardiac remodeling in a mouse model of reperfused myocardial infarction | |
| Wojtczak-Soska et al. | Soluble ST2 protein in chronic heart failure is independent of traditional factors | |
| Nadeau et al. | IL-15 improves skeletal muscle oxidative metabolism and glucose uptake in association with increased respiratory chain supercomplex formation and AMPK pathway activation | |
| Kristen et al. | Skeletal scintigraphy indicates disease severity of cardiac involvement in patients with senile systemic amyloidosis | |
| Park et al. | Association of acroosteolysis with enhanced osteoclastogenesis and higher blood levels of vascular endothelial growth factor in systemic sclerosis | |
| EP3030901B1 (en) | Methods and kits for predicting the risk of having a cardiovascular event | |
| Lakhani et al. | Developing a panel of biomarkers and miRNA in patients with myocardial infarction for early intervention strategies of heart failure in West Virginian population | |
| Kuo et al. | Age and sex differences in the relationship between neutrophil-to-lymphocyte ratio and chronic kidney disease among an adult population in Taiwan | |
| Giraldo et al. | Biomarker combination is necessary for the assessment of Gaucher disease? | |
| EP2678688B1 (en) | Method of predicting the evolution of a patient suffering of stroke | |
| Michelucci et al. | Relation of inflammatory status to major adverse cardiac events and reverse remodeling in patients undergoing cardiac resynchronization therapy | |
| Usui et al. | Endogenous muscle atrophy F-box is involved in the development of cardiac rupture after myocardial infarction | |
| CN109844529B (zh) | 用于识别未愈合的皮肤伤口以及用于监测皮肤伤口愈合的方法 | |
| CN115177730B (zh) | Ptpn22及其表达抑制剂的新用途 | |
| US20190093169A1 (en) | Biomarkers and treatments for heart failure | |
| CN107957498A (zh) | 一种含有载脂蛋白j的试剂盒及其在临床诊断中的应用 | |
| Akkus et al. | Plasma EMMPRIN levels in acute myocardial infarction and stable coronary artery disease | |
| Li et al. | Selective blockade of interleukin 6 trans-signaling depresses atrial fibrillation | |
| Wood et al. | Sodium–glucose cotransporter 2 inhibitors influence skeletal muscle pathology in patients with heart failure and reduced ejection fraction | |
| Kong et al. | Increased circulating T‑helper 22 cells in patients with dilated cardiomyopathy | |
| Ferhat et al. | Evaluation of the relationship between anti-inflammatory cytokines and adverse cardiac remodeling after myocardial infarction | |
| Cevher et al. | Evaluation of the relationship between dyssynchrony and myocardial fibrosis markers in patients with cardiac resynchronization therapy |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| CB03 | Change of inventor or designer information | ||
| CB03 | Change of inventor or designer information |
Inventor after: Cheng Xiang Inventor after: Liu Meilin Inventor after: Xia Ni Inventor after: Zha Lingfeng Inventor after: Yang Haoyi Inventor after: Li Nana Inventor before: Cheng Xiang Inventor before: Liu Meilin Inventor before: Xia Ni Inventor before: Zha Lingfeng Inventor before: Yang Haoyi |
|
| GR01 | Patent grant | ||
| GR01 | Patent grant |