Last update 01 Nov 2024

MMPs x TFPI

Last update 01 Nov 2024

Basic Info

Related Targets

MMPsTFPI

Drugs associated with MMPs x TFPI

FYK-1352

Target

MMPs x TFPI

Mechanism

MMPs inhibitors [+1]

Active Org.-

Originator Org.

Daiichi Seiyaku Co., Ltd.

Active Indication-

Inactive Indication

Neoplasms

Drug Highest PhasePending

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

W-3646

Target

MMPs x TFPI

Mechanism

MMPs inhibitors [+1]

Active Org.-

Originator Org.

Wakunaga Pharmaceutical Co., Ltd.

Active Indication-

Inactive Indication

Diabetes Mellitus, Type 2 [+1]

Drug Highest PhasePending

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with MMPs x TFPI

100 Translational Medicine associated with MMPs x TFPI

0 Patents (Medical) associated with MMPs x TFPI

191

Literatures (Medical) associated with MMPs x TFPI

01 Aug 2024·International Journal of Obesity

An epigenome-wide association study of waist circumference in Chinese monozygotic twins

Article

Author: Duan, Haiping ; Xing, Fangjie ; Tian, Huimin ; Lv, Bosen ; Wu, Yili ; Tian, Xiaocao ; Xu, Chunsheng ; Zhang, Dongfeng ; Han, Fulei ; Wang, Weijing ; Wu, Yan

OBJECTIVESCentral obesity poses significant health risks because it increases susceptibility to multiple chronic diseases. Epigenetic features such as DNA methylation may be associated with specific obesity traits, which could help us understand how genetic and environmental factors interact to influence the development of obesity. This study aims to identify DNA methylation sites associated with the waist circumference (WC) in Northern Han Chinese population, and to elucidate potential causal relationships.METHODSA total of 59 pairs of WC discordant monozygotic twins (ΔWC >0) were selected from the Qingdao Twin Registry in China. Generalized estimated equation model was employed to estimate the methylation levels of CpG sites on WC. Causal relationships between methylation and WC were assessed through the examination of family confounding factors using FAmiliaL CONfounding (ICE FALCON). Additionally, the findings of the epigenome-wide analysis were corroborated in the validation stage.RESULTSWe identified 26 CpG sites with differential methylation reached false discovery rate (FDR) < 0.05 and 22 differentially methylated regions (slk-corrected p < 0.05) strongly linked to WC. These findings provided annotations for 26 genes, with notable emphasis on MMP17, ITGA11, COL23A1, TFPI, A2ML1-AS1, MRGPRE, C2orf82, and NINJ2. ICE FALCON analysis indicated the DNA methylation of ITGA11 and TFPI had a causal effect on WC and vice versa (p < 0.05). Subsequent validation analysis successfully replicated 10 (p < 0.05) out of the 26 identified sites.CONCLUSIONSOur research has ascertained an association between specific epigenetic variations and WC in the Northern Han Chinese population. These DNA methylation features can offer fresh insights into the epigenetic regulation of obesity and WC as well as hints to plausible biological mechanisms.

31 Dec 2023·The Journal of Maternal-Fetal & Neonatal Medicine

Proteomic profile of extracellular vesicles in maternal plasma of women with fetal death

Article

Author: Bosco, Mariachiara ; Margolis, Leonid ; Gomez-Lopez, Nardhy ; Suksai, Manaphat ; Meyyazhagan, Arun ; Gotsch, Francesca ; Fitzgerald, Wendy ; Erez, Offer ; Gudicha, Dereje W. ; Chaiworapongsa, Tinnakorn ; Tarca, Adi L. ; Gallo, Dahiana M. ; Than, Nándor Gábor ; Romero, Roberto ; Jung, Eunjung

OBJECTIVESFetal death is a complication of pregnancy caused by multiple etiologies rather than being the end-result of a single disease process. Many soluble analytes in the maternal circulation, such as hormones and cytokines, have been implicated in its pathophysiology. However, changes in the protein content of extracellular vesicles (EVs), which could provide additional insight into the disease pathways of this obstetrical syndrome, have not been examined. This study aimed to characterize the proteomic profile of EVs in the plasma of pregnant women who experienced fetal death and to evaluate whether such a profile reflected the pathophysiological mechanisms of this obstetrical complication. Moreover, the proteomic results were compared to and integrated with those obtained from the soluble fraction of maternal plasma.METHODSThis retrospective case-control study included 47 women who experienced fetal death and 94 matched, healthy, pregnant controls. Proteomic analysis of 82 proteins in the EVs and the soluble fractions of maternal plasma samples was conducted by using a bead-based, multiplexed immunoassay platform. Quantile regression analysis and random forest models were implemented to assess differences in the concentration of proteins in the EV and soluble fractions and to evaluate their combined discriminatory power between clinical groups. Hierarchical cluster analysis was applied to identify subgroups of fetal death cases with similar proteomic profiles. A p-value of <.05 was used to infer significance, unless multiple testing was involved, with the false discovery rate controlled at the 10% level (q < 0.1). All statistical analyses were performed by using the R statistical language and environment-and specialized packages.RESULTSNineteen proteins (placental growth factor, macrophage migration inhibitory factor, endoglin, regulated upon activation normal T cell expressed and presumably secreted (RANTES), interleukin (IL)-6, macrophage inflammatory protein 1-alpha, urokinase plasminogen activator surface receptor, tissue factor pathway inhibitor, IL-8, E-Selectin, vascular endothelial growth factor receptor 2, pentraxin 3, IL-16, galectin-1, monocyte chemotactic protein 1, disintegrin and metalloproteinase domain-containing protein 12, insulin-like growth factor-binding protein 1, matrix metalloproteinase-1(MMP1), and CD163) were found to have different plasma concentrations (of an EV or a soluble fraction) in women with fetal death compared to controls. There was a similar pattern of change for the dysregulated proteins in the EV and soluble fractions and a positive correlation between the log₂-fold changes of proteins significant in either the EV or the soluble fraction (ρ = 0.89, p < .001). The combination of EV and soluble fraction proteins resulted in a good discriminatory model (area under the ROC curve, 82%; sensitivity, 57.5% at a 10% false-positive rate). Unsupervised clustering based on the proteins differentially expressed in either the EV or the soluble fraction of patients with fetal death relative to controls revealed three major clusters of patients.CONCLUSIONPregnant women with fetal death have different concentrations of 19 proteins in the EV and soluble fractions compared to controls, and the direction of changes in concentration was similar between fractions. The combination of EV and soluble protein concentrations revealed three different clusters of fetal death cases with distinct clinical and placental histopathological characteristics.

30 Nov 2022·Journal of Agricultural and Food Chemistry

Relationships of Matrix Metalloproteinase 1 and a Tissue Inhibitor of Metalloproteinase to Collagen Metabolism in Haliotis discus hannai

Article

Author: Jin, Tengchuan ; Cao, Min-Jie ; Chen, Yu-Lei ; Sun, Le-Chang ; Su, Le-Le ; Qiu, Xu-Jian ; Lin, Duanquan ; Zhang, Ming-Hui ; Zhang, Ling-Jing

In response to physical, chemical, and/or biological stimuli, considerable tissue self-degradation occurs in abalone, causing severe post-harvest quality loss. During this process, the extracellular matrix (ECM) is greatly degraded by endogenous proteases. The main component of the ECM is collagen, primarily type I collagen. Although the activity of matrix metalloproteinases (MMPs), which can specifically degrade collagen, is precisely regulated by tissue inhibitors of MPs (TIMPs), indicating that MMPs and TIMPs play crucial roles in the regulation of tissue self-degradation, few studies have reported the interaction between MMPs and TIMPs. In this study, we reveal collagenases to participate in postmortem tissue self-degradation of Haliotis discus hannai by degrading type I collagen. The recombinant MMP-1 catalytic domain (rMMP1c) of abalone with high purity and enzyme activity is expressed using a prokaryotic expression system. The optimum temperature and pH for rMMP1c are 37 °C and 7.0, respectively. The thermal denaturation temperature of rMMP1c is 67.0 ± 0.9 °C. Ethylenediamine tetraacetic acid (EDTA) and 1,10-phenanthroline can completely inhibit rMMP1c activity, while Ba²⁺, Ca²⁺, and Mg²⁺ can significantly elevate it. TIMP is also expressed using HEK 293F cells. Recombinant TIMP (rTIMP) shows good inhibitory activity toward rMMP1c. Inhibition kinetics analyses reveal rTIMP to be a competitive inhibitor of rMMP1c. Biolayer interferometry reveals that rTIMP can effectively bind with rMMP1c, with an equilibrium dissociation constant value of 263 nM. rMMP1c effectively degrades type I collagen γ-β-α chains in turn, and rTIMP can significantly inhibit rMMP1c degradation activity. These results provide a theoretical basis for the study of MMP and TIMP interaction and elucidate the possible mechanism for abalone tissue self-degradation.

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