更新于：2024-11-01

DSC2

更新于：2024-11-01

基本信息

别名

Cadherin family member 2、CDHF2、desmocollin 2

+ [6]

简介

Component of intercellular desmosome junctions. Involved in the interaction of plaque proteins and intermediate filaments mediating cell-cell adhesion. May contribute to epidermal cell positioning (stratification) by mediating differential adhesiveness between cells that express different isoforms.

关联

项与 DSC2 相关的药物

CN118126172

专利挖掘

靶点

DSC2

作用机制-

在研机构

珠海丽珠试剂股份有限公司

原研机构

珠海丽珠试剂股份有限公司 [+1]

在研适应症

实体瘤

非在研适应症-

最高研发阶段药物发现

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 DSC2 相关的临床结果

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100 项与 DSC2 相关的转化医学

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0 项与 DSC2 相关的专利（医药）

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315

项与 DSC2 相关的文献（医药）

2024-10-18·Circulation research

Latrophilin-2 Deletion in Cardiomyocyte Disrupts Cell Junction, Leading to D-CMP.

Article

作者: Lee, Jeongha ; Seo, Hyun Ju ; Lee, Choon-Soo ; Son, HyunJu ; Kang, Minjun ; Lee, Jaewon ; Kim, Hyo-Soo ; Cho, Hyun-Jai ; Kim, Moo-Kang ; Choi, Murim

BACKGROUNDLatrophilin-2 (Lphn2), an adhesive GPCR (G protein-coupled receptor), was found to be a specific marker of cardiac progenitors during the differentiation of pluripotent stem cells into cardiomyocytes or during embryonic heart development in our previous studies. Its role in adult heart physiology, however, remains unclear.METHODSThe embryonic lethality resulting from Lphn2 deletion necessitates the establishment of cardiomyocyte-specific, tamoxifen-inducible Lphn2 knockout mice, which was achieved by crossing Lphn2^flox/flox mice with mice having MerCreMer (tamoxifen-inducible Cre recombinase) under the α-myosin heavy chain promoter.RESULTSTamoxifen treatment for several days completely suppressed Lphn2 expression, specifically in the myocardium, and induced the dilated cardiomyopathy (D-CMP) phenotype with serious arrhythmia and sudden death in a short period of time. Transmission electron microscopy showed mitochondrial abnormalities, blurred Z-discs, and dehiscent myofibrils. The D-CMP phenotype, or heart failure, worsened during myocardial infarction. In a mechanistic study of D-CMP, Lphn2 knockout suppressed PGC-1α and mitochondrial dysfunction, leading to the accumulation of reactive oxygen species and the global suppression of junctional molecules, such as N-cadherin (adherens junction), DSC-2 (desmocollin-2; desmosome), and connexin-43 (gap junction), leading to the dehiscence of cardiac myofibers and serious arrhythmia. In an experimental therapeutic trial, activators of p38-MAPK, which is a downstream signaling molecule of Lphn2, remarkably rescued the D-CMP phenotype of Lphn2 knockout in the heart by restoring PGC-1α and mitochondrial function and recovering global junctional proteins.CONCLUSIONSLphn2 is a critical regulator of heart integrity by controlling mitochondrial functions and cell-to-cell junctions in cardiomyocytes. Its deficiency leads to D-CMP, which can be rescued by activators of the p38-MAPK pathway.

2024-10-01·Journal of Molecular and Cellular Cardiology

Arrhythmogenic cardiomyopathy-related cadherin variants affect desmosomal binding kinetics

Article

作者: Anselmetti, Dario ; Walhorn, Volker ; Steinecker, Sylvia M ; Göz, Manuel ; Pohl, Greta ; Milting, Hendrik

Cadherins are calcium dependent adhesion proteins that establish and maintain the intercellular mechanical contact by bridging the gap between adjacent cells. Desmoglein-2 (Dsg2) and desmocollin-2 (Dsc2) are tissue specific cadherin isoforms of the cell-cell contact in cardiac desmosomes. Mutations in the DSG2-gene and in the DSC2-gene are related to arrhythmogenic right ventricular cardiomyopathy (ARVC) a rare but severe heart muscle disease. Here, several possible homophilic and heterophilic binding interactions of wild-type Dsg2, wild-type Dsc2, as well as one Dsg2- and two Dsc2-variants, each associated with ARVC, are investigated. Using single molecule force spectroscopy (SMFS) with atomic force microscopy (AFM) and applying Jarzynski's equality the kinetics and thermodynamics of Dsg2/Dsc2 interaction can be determined. The free energy landscape of Dsg2/Dsc2 dimerization exposes a high activation energy barrier, which is in line with the proposed strand-swapping binding motif. Although the binding motif is not affected by any of the mutations, the binding kinetics of the interactions differ significantly from the wild-type. While wild-type cadherins exhibit an average complex lifetime of approx. 0.3 s interactions involving a variant consistently show - lifetimes that are substantially larger. The lifetimes of the wild-type interactions give rise to the picture of a dynamic adhesion interface consisting of continuously dissociating and (re)associating molecular bonds, while the delayed binding kinetics of interactions involving an ARVC-associated variant might be part of the pathogenesis. Our data provide a comprehensive and consistent thermodynamic and kinetic description of cardiac cadherin binding, allowing detailed insight into the molecular mechanisms of cell adhesion.

2024-09-27·Medicine

Unveiling the glycolysis in sepsis: Integrated bioinformatics and machine learning analysis identifies crucial roles for IER3, DSC2, and PPARG in disease pathogenesis

Article

作者: Yu, Tian ; Cui, Dongqing

Sepsis, a multifaceted syndrome driven by an imbalanced host response to infection, remains a significant medical challenge. At its core lies the pivotal role of glycolysis, orchestrating immune responses especially in severe sepsis. The intertwined dynamics between glycolysis, sepsis, and immunity, however, have gaps in knowledge with several Crucial genes still shrouded in ambiguity. We harvested transcriptomic profiles from the peripheral blood of 107 septic patients juxtaposed against 29 healthy controls. Delving into this dataset, differential expression analysis shed light on genes distinctly linked to glycolysis in both cohorts. Harnessing the prowess of LASSO regression and SVM-RFE, we isolated Crucial genes, paving the way for a sepsis risk prediction model, subsequently vetted via Calibration and decision curve analysis. Using the CIBERSORT algorithm, we further mapped 22 immune cell subtypes within the septic samples, establishing potential interactions with the delineated Crucial genes. Our efforts unveiled 21 genes intricately tied to glycolysis that exhibited differential expression patterns. Gene set enrichment analysis (GSEA) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses offered insights, spotlighting pathways predominantly associated with oxidative phosphorylation, PPAR signaling pathway, Glycolysis/Gluconeogenesis and HIF-1 signaling pathway. Among the myriad genes, IER3, DSC2, and PPARG emerged as linchpins, their prominence in sepsis further validated through ROC analytics. These sentinel genes demonstrated profound affiliations with various immune cell facets, bridging the complex terrain of glycolysis, sepsis, and immune responses. In line with our endeavor to “unveil the glycolysis in sepsis,” the discovery of IER3, DSC2, and PPARG reinforces their cardinal roles in sepsis pathogenesis. These revelations accentuate the intricate dance between glycolysis and immunological shifts in septic conditions, offering novel avenues for therapeutic interventions.