Serine protease x Collagen

Last update 23 Jan 2025

Basic Info

Related Targets

Serine proteaseCollagen

Drugs associated with Serine protease x Collagen

QRX-004

Target

Collagen x Serine protease

Mechanism

Collagen modulators [+1]

Active Org.

Quoin Pharmaceuticals, Inc.

Originator Org.

Quoin Pharmaceuticals, Inc.

Active Indication

Epidermolysis Bullosa

Inactive Indication-

Drug Highest PhasePhase 2

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with Serine protease x Collagen

100 Translational Medicine associated with Serine protease x Collagen

0 Patents (Medical) associated with Serine protease x Collagen

Literatures (Medical) associated with Serine protease x Collagen

01 Dec 2024·International Immunopharmacology

PAI-1 influences and curcumin destabilizes MMP-2, MMP-9 and basement membrane proteins during lung injury and fibrosis

Article

Author: Moideen, Fathimath Muneesa ; Alghofaili, Fayez ; Bhandary, Yashodhar P ; Charavu, Rakshitha ; Rahamathulla, Mohamudha Parveen ; Sha, Mohemmed

One of the characteristic feature of idiopathic pulmonary fibrosis is an imbalanced fibrinolytic system. Plasminogen activator inhibitor-1 (PAI-1), an essential serine protease in the fibrinolytic system, has an anti-fibrotic tendency in some organs and a pro-fibrotic nature in others. Curcumin is reported to regulate the fibrinolytic system. In this study, we sought to determine how curcumin affected alterations in tissue remodelling mediated by PAI-1 in lung fibrosis. For in vitro studies, NIH3T3 fibroblasts were either exposed to TGF-β or overexpressed with PAI-1, and/or treated with curcumin. For in vivo studies, C57BL/6 mice were either instilled with bleomycin, overexpressed with PAI-1, and/or intervened with curcumin. Protein and gene expression studies were performed by western blotting and RT-PCR techniques, respectively. Curcumin intervention, in vitro and in vivo, could inhibit the the expression of collagen, fibronectin, MMP-2, and MMP-9, which was otherwise elevated by TGF-β or bleomycin. In conclusion, curcumin reduces pulmonary fibrosis by suppressing excessive basement membrane protein deposition and, likely, preventing the thickening of the alveolar septum.

01 Oct 2018·Journal of Assisted Reproduction and GeneticsQ3 · MEDICINE

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

Q3 · MEDICINE

Article

Author: Wang, Fan ; Ord, Teri ; Senapati, Suneeta ; 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.

01 Jul 2017·Allergology International

Human eosinophils constitutively express a unique serine protease, PRSS33

Article

Author: Fujisawa, Takao ; Okada, Naoko ; Karasuyama, Hajime ; Morita, Hideaki ; Saito, Hirohisa ; Toyama, Sumika ; Matsumoto, Kenji ; Matsuda, Akio ; Nakae, Susumu

BACKGROUNDEosinophils play important roles in asthma, especially airway remodeling, by producing various granule proteins, chemical mediators, cytokines, chemokines and proteases. However, protease production by eosinophils is not fully understood. In the present study, we investigated the production of eosinophil-specific proteases/proteinases by transcriptome analysis.METHODSHuman eosinophils and other cells were purified from peripheral blood by density gradient sedimentation and negative/positive selections using immunomagnetic beads. Protease/proteinase expression in eosinophils and release into the supernatant were evaluated by microarray analysis, qPCR, ELISA, flow cytometry and immunofluorescence staining before and after stimulation with eosinophil-activating cytokines and secretagogues. mRNAs for extracellular matrix proteins in human normal fibroblasts were measured by qPCR after exposure to recombinant protease serine 33 (PRSS33) protein (rPRSS33), created with a baculovirus system.RESULTSHuman eosinophils expressed relatively high levels of mRNA for metalloproteinase 25 (MMP25), a disintegrin and metalloprotease 8 (ADAM8), ADAM10, ADAM19 and PRSS33. Expression of PRSS33 was the highest and eosinophil-specific. PRSS33 mRNA expression was not affected by eosinophil-activating cytokines. Immunofluorescence staining showed that PRSS33 was co-localized with an eosinophil granule protein. PRSS33 was not detected in the culture supernatant of eosinophils even after stimulation with secretagogues, but its cell surface expression was increased. rPRSS33 stimulation of human fibroblasts increased expression of collagen and fibronectin mRNAs, at least in part via protease-activated receptor-2 activation.CONCLUSIONSActivated eosinophils may induce fibroblast extracellular matrix protein synthesis via cell surface expression of PRSS33, which would at least partly explain eosinophils' role(s) in airway remodeling.

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