Heparin-binding epidermal growth factor-like growth factor (HB-EGF) and proteolytic processing by a disintegrin and metalloproteinases (ADAM): A regulator of several pathways

Taylor, Sean R.; Markesbery, M.G.; Harding, Paul A.

doi:10.1016/j.semcdb.2014.03.004

Cited by 61 publications

(61 citation statements)

References 145 publications

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“…On the contrary, SVF cells cultured in functionalized ELR mainly upregulated the release of factors known as pro-angiogenic (70% of the upregulated factors were proangiogenic) (e.g. Monocyte chemoattractant protein-1 (MCP-1) [37], Insulin Growth Factor Binding Protein-2 (IGFBP-2) [38], Heparin-binding Epidermal Growth Factor (HB-EGF) [39], VEGF [40], Interleukin-1β (IL-1β) [41], and urokinase-type plasminogen activator (uPA) [42]). Among all the investigated factors, SVF cells upregulated the expression of proteases, namely Dipeptidyl peptidase-4 (DPPIV) and Matrix Metallopeptidase 9 (MMP-9), and of growth factors, namely Platelet Factor 4 (PF4), persephin, and endothelin-a in both RR and NF closed structure hydrogels (Suppl.…”

Section: In Vitro Culture Of Elrs-based Constructsmentioning

confidence: 99%

Control of angiogenesis and host response by modulating the cell adhesion properties of an Elastin-Like Recombinamer-based hydrogel

et al. 2017

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The control of the in vivo vascularization of engineered tissue substitutes is essential in order to obtain either a rapid induction or a complete inhibition of the process (e.g. in muscles and hyaline-cartilage, respectively). Among the several polymers available, Elastin-Like Recombinamers (ELRs)-based hydrogel stands out as a promising material for tissue engineering thanks to its viscoelastic properties, non-toxicity, and non-immunogenicity. In this study, we aimed to modulate the high angiogenic potential of adipose tissue-derived stromal vascular fraction (SVF) cells, predominantly composed of endothelial/mural and mesenchymal cells, by simply varying the cell adhesion properties of ELRs-hydrogels. Human SVF cells, embedded in RGD-REDVbioactivated or unmodified ELRs-hydrogels, were implanted in rat subcutaneous pockets either immediately or upon 5-day-culture in perfusion-bioreactors. Perfusionbased culture enhanced the endothelial cell cord-like-organization and the release of pro-angiogenic factors in functionalized constructs. While in vivo vascularization and host cell infiltration within the bioactivated gels were highly enhanced, the two processes were strongly inhibited in non-functionalized hydrogels up to 28 days. ELRsbased hydrogels showed a great potential to determine the successful integration of engineered substitutes thanks to their capacity to finely control the angiogenic/inflammation process at the recipient site, even in presence of SVF cells.

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Section: In Vitro Culture Of Elrs-based Constructsmentioning

confidence: 99%

Control of angiogenesis and host response by modulating the cell adhesion properties of an Elastin-Like Recombinamer-based hydrogel

et al. 2017

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“…Most of the functions described for sHB-EGF correlate with its ability to activate EGFR and downstream pathways, including PI3 kinase, Akt, mTOR, ERK, and MEK, as well as cross talk with IGF receptor 1 (IGFR1) signaling (58,86). While we have not delineated the entire signaling pathway in muscle, we have shown that sHB-EGF activates the muscle EGFR signaling and increases Akt phosphorylation.…”

Section: Discussionmentioning

confidence: 71%

Soluble Heparin Binding Epidermal Growth Factor-Like Growth Factor Is a Regulator of GALGT2 Expression and GALGT2-Dependent Muscle and Neuromuscular Phenotypes

Cramer

Martin

2019

Molecular and Cellular Biology

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GALGT2 (also B4GALNT2) encodes a glycosyltransferase that is normally confined to the neuromuscular and myotendinous junction in adult skeletal muscle. GALGT2 overexpression in muscle can inhibit muscular dystrophy in mouse models of the disease by inducing the overexpression of surrogate muscle proteins, including utrophin, agrin, laminins, and integrins. Despite its well-documented biological properties, little is known about the endogenous regulation of muscle GALGT2 expression. Here, we demonstrate that epidermal growth factor receptor (EGFR) ligands can activate the human GALGT2 promoter. Overexpression of one such ligand, soluble heparin-binding EGF-like growth factor (sHB-EGF), also stimulated mouse muscle Galgt2 gene expression and expression of GALGT2-inducible surrogate muscle genes. Deletion analysis of the GALGT2 promoter identified a 45-bp region containing a TFAP4-binding site that was required for sHB-EGF activation. sHB-EGF increased TFAP4 binding to this site in muscle cells and increased endogenous Tfap4 gene expression. sHB-EGF also increased muscle EGFR protein expression and activated EGFR-Akt signaling. sHB-EGF expression was concentrated at the neuromuscular junction, and Hbegf deletion reduced Galgt2-dependent synaptic glycosylation. Hbegf deletion also mimicked Galgt2-dependent neuromuscular and muscular dystrophy phenotypes. These data demonstrate that sHB-EGF is an endogenous regulator of muscle Galgt2 gene expression and can mimic Galgt2-dependent muscle phenotypes.

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“…Processing of proHB-EGF by ADAM proteins releases the active form that binds and activates EGFR (20). Previous studies in mesangial cells suggest that glucose-induced proteolytic processing of HB-EGF requires Src activation (27).…”

Section: Glucose-induced B-cell Proliferation Is Dependent On Src Upsmentioning

confidence: 99%

“…In previous studies we discovered that expression of the heparin-binding epidermal growth factor (EGF)-like growth factor (HB-EGF) is up-regulated in islets from nutrient-infused rats, and that exogenous HB-EGF stimulates replication of MIN6 cells and primary rat b cells (18). HB-EGF is a member of the EGF family synthesized as a membraneanchored precursor that can be processed by the action of a disintegrins and metalloproteinases (ADAM) to release the soluble active form (20). HB-EGF induces phosphorylation of EGFR and subsequent activation of a downstream signaling cascade including MAPK and PI3K/AKT.…”

Section: Introductionmentioning

confidence: 99%

HB-EGF Signaling is Required for Glucose-Induced Pancreatic β-Cell Proliferation in Rats

Maachi

Fergusson

Ethier

et al. 2019

Preprint

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The molecular mechanisms of β-cell compensation to metabolic stress are poorly understood. We previously observed that nutrient-induced β-cell proliferation in rats is dependent on Epidermal Growth Factor Receptor (EGFR) signaling. The aim of this study was to determine the role of the EGFR ligand Heparin-Binding EGF-like Growth Factor (HB-EGF) in the β-cell proliferative response to glucose, a β-cell mitogen and key regulator of β-cell mass in response to increased insulin demand. We show that exposure of isolated rat and human islets to HB-EGF stimulates β-cell proliferation. In rat islets, inhibition of EGFR or HB-EGF blocks the proliferative response not only to HB-EGF but also to glucose. Furthermore, knockdown of HB-EGF in rat islets blocks β-cell proliferation in response to glucose ex vivo and in vivo in transplanted glucose-infused rats. Mechanistically, we demonstrate that HB-EGF mRNA levels are increased in β cells in response to glucose in a Carbohydrate Response Element Binding Protein (ChREBP)-dependent manner. In addition, chromatin-immunoprecipitation studies identified ChREBP binding sites in proximity to the HB-EGF gene. Finally, inhibition of Src family kinases, known to be involved in HB-EGF processing, abrogated glucose-induced β-cell proliferation. Our findings identify a novel glucose/HB-EGF/EGFR axis implicated in β-cell compensation to increased metabolic demand.

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Heparin-binding epidermal growth factor-like growth factor (HB-EGF) and proteolytic processing by a disintegrin and metalloproteinases (ADAM): A regulator of several pathways

Cited by 61 publications

References 145 publications

Control of angiogenesis and host response by modulating the cell adhesion properties of an Elastin-Like Recombinamer-based hydrogel

Control of angiogenesis and host response by modulating the cell adhesion properties of an Elastin-Like Recombinamer-based hydrogel

Soluble Heparin Binding Epidermal Growth Factor-Like Growth Factor Is a Regulator of GALGT2 Expression and GALGT2-Dependent Muscle and Neuromuscular Phenotypes

HB-EGF Signaling is Required for Glucose-Induced Pancreatic β-Cell Proliferation in Rats

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