更新于：2024-11-01

Serine protease x Collagen

更新于：2024-11-01

基本信息

关联

项与 Serine protease x Collagen 相关的药物

QRX-004

靶点

Collagen x Serine protease

作用机制

胶原蛋白调节剂 [+1]

在研机构

Quoin Pharmaceuticals, Inc.

原研机构

Quoin Pharmaceuticals, Inc.

在研适应症

大疱性表皮松解

非在研适应症-

最高研发阶段临床2期

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 Serine protease x Collagen 相关的临床结果

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100 项与 Serine protease x Collagen 相关的转化医学

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0 项与 Serine protease x Collagen 相关的专利（医药）

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项与 Serine protease x Collagen 相关的文献（医药）

2018-10-01·Journal of Assisted Reproduction and Genetics3区 · 医学

Superovulation alters the expression of endometrial genes critical to tissue remodeling and placentation

3区 · 医学

Article

作者: Wang, Fan ; Senapati, Suneeta ; Ord, Teri ; Feng, Rui ; Mainigi, Monica ; Coutifaris, Christos

PURPOSEEpidemiologic data suggest that in vitro fertilization (IVF) is associated with an increased risk of disorders of placentation including preeclampsia and fetal growth restriction. Specifically, studies have demonstrated that singleton pregnancies conceived following a fresh embryo transfer are at an increased risk of delivering an infant with low birth weight compared to those conceived following a frozen embryo transfer. The mechanism responsible for this association remains unclear. Procedures utilized in IVF have also been linked with epigenetic changes and gene expression changes in both fetal and maternal tissues. Data suggest that modifications in the maternal endometrium can lead to disordered trophoblast invasion and placentation. This study examines the effect of ovarian stimulation on endometrial gene expression and DNA methylation during the window of implantation to examine potential pathways playing a role in the adverse outcomes associated with IVF.METHODSEndometrial biopsies were obtained from oocyte donors and age-matched naturally cycling women 11 days following oocyte retrieval in donors or 12 days following luteinizing hormone (LH) surge in naturally cycling women. Global gene expression was analyzed via Affymetrix Human Gene 1.1 ST array and confirmed with RT-qPCR. DNA methylation was assessed with the Infinium DNA methylation 450 K BeadChip.RESULTSAnalysis of endometrial gene expression from 23 women (11 oocyte donors and 12 controls) demonstrated 165 genes with a greater than twofold change in expression between donors and controls. While there were 785 genes with significant differential methylation in the endometrium of donors when compared with control subjects, none of the genes with altered expression showed significant changes in DNA methylation. Analysis of the differentially expressed genes showed enrichment for genes involved in endometrial remodeling including PLAT, HSPE2, MMP2, and TIMP1. Validation studies using RT-qPCR found a 73% reduction in expression of heparanase 2 (HSPE2) an enzyme associated with both angiogenesis and cell invasion, a greater than twofold increase in tissue-type plasminogen activator (PLAT), a serine protease participating in matrix degradation, and a 70% increase in MMP2, a gelatinase involved in collagen and fibronectin breakdown.CONCLUSIONSSuperovulation alters expression of genes critical to endometrial remodeling during early implantation. Such changes could lead to altered trophoblast migration and impaired endovascular invasion. These findings offer a potential mechanism for the adverse perinatal outcomes observed following embryo transfer during fresh IVF cycles.

2016-10-01·Veterinary Parasitology2区 · 农林科学

The induction of the collagen capsule synthesis by Trichinella spiralis is closely related to protease-activated receptor 2

2区 · 农林科学

Article

作者: Kang, Shin Ae ; Cho, Min Kyoung ; Kim, Bo Young ; Yu, Hak Sun ; Park, Mi Kyung

The muscle-stage larvae of the parasite Trichinella spiralis have the ability to survive within host muscle tissue by virtue of the formation a nurse cell-parasite complex, which is surrounded by collagen. The formation of the complex is initiated by excretory-secretory (ES) proteins produced by the parasite. To determine the mechanisms underlying collagen capsule formation, we investigated the expression levels of several types of collagen genes and TGF-βI signaling-related genes (Smad2 and Smad3) in muscle cells. Synthesis of type I, IV, and VI collagen, which are major constituents of the collagen capsule, significantly increased during T. spiralis infection. In addition, we found that expression of the protease-activated receptor 2 (PAR2) gene was significantly increased during this period. Expression levels of the collagen genes and TGF-βI, Smad2, and Smad3 were induced by ES proteins and a PAR2 agonist, whereas their enhanced expression levels were reduced by a PAR2 antagonist and serine protease inhibitors. To evaluate the involvement of PAR2 during T. spiralis infection in vivo, we infected wild-type and PAR2 knockout (KO) mice with T. spiralis. Expression levels of type I, IV, and VI collagen genes and TGF-βI signaling-related genes (Smad2 and Smad3) were also decreased in the PAR2 KO mice. Phosphorylation of Smad2/3, which was increased by T. spiralis infection, was significantly diminished in the PAR2 KO mice. In conclusion, ES proteins containing serine protease most likely activate collagen synthesis via PAR2 and TGF-βI signaling, and this event could influence collagen capsule formation.

2014-06-01·Arthritis & Rheumatology1区 · 医学

Activation of Matrix Metalloproteinases 2, 9, and 13 by Activated Protein C in Human Osteoarthritic Cartilage Chondrocytes

1区 · 医学

Article

作者: Moradi, Babak ; Jackson, Christopher J. ; Jackson, Miriam T. ; Little, Christopher B. ; Smith, Margaret M.

ObjectiveLevels of activated protein C (APC) are elevated in the synovial fluid of patients with osteoarthritis (OA), and increased APC levels are correlated with the levels of active matrix metalloproteinase 2 (MMP‐2). This study sought to investigate whether APC is a relevant protein for activation of MMPs in the degradation of human OA cartilage, and to elucidate its mechanisms of action.MethodsHuman articular cartilage was cultured with or without interleukin‐1α (IL‐1α), in the presence or absence of APC or protein C, and an MMP or serine proteinase inhibitor. Aggrecan and collagen release and chondrocyte gene expression levels were quantified. Aggrecanase and MMP cleavage of aggrecan was examined with neoepitope‐specific antibodies, and MMP activity was measured using gelatin zymography and fluorogenic peptide assay.ResultsIn human OA cartilage, APC induced aggrecan and collagen release, whereas in non‐OA cartilage, costimulation with IL‐1α was required. Inhibition of MMP activity reduced APC‐induced cartilage proteolysis, and MMP‐induced aggrecanolysis was confirmed by Western blotting. In cultures with APC alone, the activity of MMPs 2, 9, and 13 was significantly increased in OA cartilage, although APC could not directly activate MMPs 2 or 9. Expression of MMP1, MMP2, MMP9, MMP13, TIMP1, and TIMP3 was not altered by APC in OA cartilage. Human OA chondrocytes expressed messenger RNA for protein C, endothelial protein C receptor, thrombomodulin, and protease‐activated receptor 1, but these were unaltered or down‐regulated by APC. The induction of MMP activation and cartilage degradation by APC was dependent on its serine protease activity.ConclusionAPC is a physiologically relevant activator of MMPs and cartilage breakdown in human OA. The effects of APC are dependent on its proteolytic activity and as‐yet‐undefined cell and/or cartilage matrix factors, and inhibition of this pathway may provide a novel therapeutic target to halt the progression of cartilage damage in OA.