Heparanase Localization during Palatogenesis in Mice

Hirata, Azumi; Katayama, Kentaro; Tsuji, Takehito; Natsume, Nagato; Sugahara, Toshio; Koga, Yuichi; Takano, Kazufumi; Otsuki, Yoshinori; Nakamura, Hiroaki

doi:10.1155/2013/760236

Cited by 5 publications

(4 citation statements)

References 41 publications

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“…MMPs are sheddases that are capable of cleaving syndecans from the cell surface. Multiple studies have reported that MMP-1, -2, -3, -7, and -9 are involved with upregulation of HPSE in various cell lines (32,(39)(40)(41). Additionally, decreasing the levels of MMP-9 has been shown to ameliorate herpes simplex keratitis in vitro and in vivo (42,43).…”

Section: Resultsmentioning

confidence: 99%

Heparanase-Regulated Syndecan-1 Shedding Facilitates Herpes Simplex Virus 1 Egress

Hadigal

Koganti

Yadavalli

et al. 2020

J Virol

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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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Section: Resultsmentioning

confidence: 99%

Heparanase-Regulated Syndecan-1 Shedding Facilitates Herpes Simplex Virus 1 Egress

Hadigal

Koganti

Yadavalli

et al. 2020

J Virol

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“…Furthermore, Tgfβ-3-and Egfr-knockout mice, which display a cleft palate phenotype, have decreased or absent MMP expression in the MEE or MES (Miettinen et al, 1999;Blavier et al, 2001). Heparanase has also been detected in the MEE and MES and co-localized with MMPs -2, -3, and -9 (Hirata et al, 2013). MMP-25 can cleave only collagen IV and, in terms of substrates, displays more similarities to MMP-3 than other MT-MMPs (English et al, 2001).…”

Section: The Roles Of Mmps and Timps In Palatogenesismentioning

confidence: 99%

Extracellular Matrix Composition and Remodeling: Current Perspectives on Secondary Palate Formation, Cleft Lip/Palate, and Palatal Reconstruction

Paiva

Maas

Santos

et al. 2019

Front. Cell Dev. Biol.

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Craniofacial development comprises a complex process in humans in which failures or disturbances frequently lead to congenital anomalies. Cleft lip with/without palate (CL/P) is a common congenital anomaly that occurs due to variations in craniofacial development genes, and may occur as part of a syndrome, or more commonly in isolated forms (non-syndromic). The etiology of CL/P is multifactorial with genes, environmental factors, and their potential interactions contributing to the condition. Rehabilitation of CL/P patients requires a multidisciplinary team to perform the multiple surgical, dental, and psychological interventions required throughout the patient's life. Despite progress, lip/palatal reconstruction is still a major treatment challenge. Genetic mutations and polymorphisms in several genes, including extracellular matrix (ECM) genes, soluble factors, and enzymes responsible for ECM remodeling (e.g., metalloproteinases), have been suggested to play a role in the etiology of CL/P; hence, these may be considered likely targets for the development of new preventive and/or therapeutic strategies. In this context, investigations are being conducted on new therapeutic approaches based on tissue bioengineering, associating stem cells with biomaterials, signaling molecules, and innovative technologies. In this review, we discuss the role of genes involved in ECM composition and remodeling during secondary palate formation and pathogenesis and genetic etiology of CL/P. We also discuss potential therapeutic approaches using bioactive molecules and principles of tissue bioengineering for state-of-the-art CL/P repair and palatal reconstruction.

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“…CSPGs, DSPGs, HSPGs, and HA are all enriched in developing palatal shelves [30][31][32][33]. The GAG chains, predominantly HA, which are accumulated in palatal mesenchyme and combined a large number of water molecules, are considered as the main driving force for palatal expansion and elevation.…”

Section: Introductionmentioning

confidence: 99%

Deficiency of Fam20b-Catalyzed Glycosaminoglycan Chain Synthesis in Neural Crest Leads to Cleft Palate

Chen

et al. 2023

IJMS

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Cleft palate is one of the most common birth defects. Previous studies revealed that multiple factors, including impaired intracellular or intercellular signals, and incoordination of oral organs led to cleft palate, but were little concerned about the contribution of the extracellular matrix (ECM) during palatogenesis. Proteoglycans (PGs) are one of the important macromolecules in the ECM. They exert biological functions through one or more glycosaminoglycan (GAG) chains attached to core proteins. The family with sequence similarity 20 member b (Fam20b) are newly identified kinase-phosphorylating xylose residues that promote the correct assembly of the tetrasaccharide linkage region by creating a premise for GAG chain elongation. In this study, we explored the function of GAG chains in palate development through Wnt1-Cre; Fam20bf/f mice, which exhibited complete cleft palate, malformed tongue, and micrognathia. In contrast, Osr2-Cre; Fam20bf/f mice, in which Fam20b was deleted only in palatal mesenchyme, showed no abnormality, suggesting that failed palatal elevation in Wnt1-Cre; Fam20bf/f mice was secondary to micrognathia. In addition, the reduced GAG chains promoted the apoptosis of palatal cells, primarily resulting in reduced cell density and decreased palatal volume. The suppressed BMP signaling and reduced mineralization indicated an impaired osteogenesis of palatine, which could be rescued partially by constitutively active Bmpr1a. Together, our study highlighted the key role of GAG chains in palate morphogenesis.

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Heparanase Localization during Palatogenesis in Mice

Cited by 5 publications

References 41 publications

Heparanase-Regulated Syndecan-1 Shedding Facilitates Herpes Simplex Virus 1 Egress

Heparanase-Regulated Syndecan-1 Shedding Facilitates Herpes Simplex Virus 1 Egress

Extracellular Matrix Composition and Remodeling: Current Perspectives on Secondary Palate Formation, Cleft Lip/Palate, and Palatal Reconstruction

Deficiency of Fam20b-Catalyzed Glycosaminoglycan Chain Synthesis in Neural Crest Leads to Cleft Palate

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