Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.17 (MMP-3)
 3,419 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Palatogenesis is directed by epithelial-mesenchymal interactions and results partly from remodeling of the extracellular matrix (ECM) of the palatal shelves. Here, we assessed heparanase distribution in developing mouse palates. No heparanase was observed in the vertically oriented palatal shelves in early stages of palate formation. As palate formation progressed, the palatal shelves were reorganized and arranged horizontally above the tongue, and heparanase localized to the epithelial cells of these shelves. When the palatal bilateral shelves first made contact, the heparanase localized to epithelial cells at the tips of shelves. Later in fusing palatal shelves, the cells of the medial epithelial seam (MES) were labeled with intense heparanase signal. In contrast, the basement membrane heparan sulfate (HS) was scarcely observed in the palatal shelves in contact. Moreover, perlecan labeling was sparse in the basement membrane of the MES, on which laminin and type IV collagen were observed. Moreover, we assessed the distribution of matrix metalloproteinase- (MMP-) 9, MMP-2, and MMP-3 in developing mouse palates and these MMPs were observed in the MES. Our findings indicated that heparanase was important for palate formation because it mediated degradation of the ECM of palatal shelves. Heparanase may, in concert with other proteases, participate in the regression of the MES.
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PMID:Heparanase localization during palatogenesis in mice. 2350 75

Herpes simplex virus 1 (HSV-1) can infect virtually all cell types in vitro An important reason lies in its ability to exploit heparan sulfate (HS) for attachment to cells. HS is a ubiquitous glycosaminoglycan located on the cell surface and tethered to proteoglycans such as syndecan-1. Previously, we have shown that heparanase (HPSE) facilitates the release of viral particles by cleaving HS. Here, we demonstrate that HPSE is a master regulator where, in addition to directly enabling viral release via HS removal, it also facilitates cleavage of HS-containing ectodomains of syndecan-1, thereby further enhancing HSV-1 egress from infected cells. Syndecan-1 cleavage is mediated by upregulation of matrix metalloproteases (MMPs) that accompanies higher HPSE expression in infected cells. By overexpressing HPSE, we have identified MMP-3 and MMP-7 as important sheddases of syndecan-1 shedding in corneal epithelial cells, which are natural targets of HSV-1 infection. MMP-3 and MMP-7 were also naturally upregulated during HSV-1 infection. Altogether, this paper shows a new connection between HSV-1 release and syndecan-1 shedding, a phenomenon that is regulated by HPSE and executed by the MMPs. Our results also identify new molecular markers for HSV-1 infection and new targets for future interventions.IMPORTANCE HSV-1 is a common cause of recurrent viral infections in humans. The virus can cause a range of mucosal pathologies. Efficient viral egress from infected cells is an important step for HSV-1 transmission and virus-associated pathologies. Host mechanisms that contribute to HSV-1 egress from infected cells are poorly understood. Syndecan-1 is a common heparan sulfate proteoglycan expressed by many natural target cells. Despite its known connection with heparanase, a recently identified mediator of HSV-1 release, syndecan-1 has not been previously investigated in HSV-1 release. In this study, we demonstrate that the shedding of syndecan-1 by MMP-3 and MMP-7 supports viral egress. We show that the mechanism behind the activation of these MMPs is mediated by heparanase, which is upregulated upon HSV-1 infection. Our study elucidates a new connection between HSV-1 egress, heparanase, and matrix metallopeptidases; identifies new molecular markers of infection; and provides potential new targets for therapeutic interventions.
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PMID:Heparanase-Regulated Syndecan-1 Shedding Facilitates Herpes Simplex Virus 1 Egress. 3182 1