The role of basement membrane laminins in vascular function

Hannocks, Melanie-Jane; Song, Jian; Zhang, Xueli; Russo, Jacopo Di; Luik, Anna-Liisa; Burmeister, Miriam; Gerwien, Hanna; Sorokin, Lydia

doi:10.1016/j.biocel.2020.105823

Cited by 28 publications

(26 citation statements)

References 59 publications

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“…Laminin β2‐null mice develop postnatal kidney defects and a neuromuscular junction phenotype. In contrast to all these laminin mutant mice, which either die during embryogenesis or display postnatal severe phenotypes, mice devoid of laminin γ3 chain only show minor abnormalities [55,494,495].…”

Section: Laminins: the Three‐armed Ecm Adhesion Proteinsmentioning

confidence: 99%

A guide to the composition and functions of the extracellular matrix

et al. 2021

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Extracellular matrix (ECM) is a dynamic 3‐dimensional network of macromolecules that provides structural support for the cells and tissues. Accumulated knowledge clearly demonstrated over the last decade that ECM plays key regulatory roles since it orchestrates cell signaling, functions, properties and morphology. Extracellularly secreted as well as cell‐bound factors are among the major members of the ECM family. Proteins/glycoproteins, such as collagens, elastin, laminins and tenascins, proteoglycans and glycosaminoglycans, hyaluronan, and their cell receptors such as CD44 and integrins, responsible for cell adhesion, comprise a well‐organized functional network with significant roles in health and disease. On the other hand, enzymes such as matrix metalloproteinases and specific glycosidases including heparanase and hyaluronidases contribute to matrix remodeling and affect human health. Several cell processes and functions, among them cell proliferation and survival, migration, differentiation, autophagy, angiogenesis, and immunity regulation are affected by certain matrix components. Structural alterations have been also well associated with disease progression. This guide on the composition and functions of the ECM gives a broad overview of the matrisome, the major ECM macromolecules, and their interaction networks within the ECM and with the cell surface, summarizes their main structural features and their roles in tissue organization and cell functions, and emphasizes the importance of specific ECM constituents in disease development and progression as well as the advances in molecular targeting of ECM to design new therapeutic strategies.

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Section: Laminins: the Three‐armed Ecm Adhesion Proteinsmentioning

confidence: 99%

A guide to the composition and functions of the extracellular matrix

et al. 2021

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“…A central, but commonly overlooked, structural and functional element of blood vessels is the endothelial basement membrane (BM), a self-assembled layer of highly specialized glycoproteins, produced by ECs and pericytes, that underlies the former and encases the latter [ 18 ]. Endothelial BMs are not only structural scaffolds, but also contribute to the mechanical properties of blood vessels and transmit signals to endothelial and perivascular cells that may regulate blood flow and nutrient and oxygen supply [ 19 ].…”

Section: Introductionmentioning

confidence: 99%

“…The biological role of the laminins is largely defined by their α-chain interaction with integrin and non-integrin receptors [ 24 , 25 ]. Laminin α4 and α5 chains combine with laminin β1 and γ1 chains to form laminins 411 and 511, respectively, found in endothelial and smooth muscle BMs [ 18 ].…”

Section: Introductionmentioning

confidence: 99%

Superoxide Dismutase-3 Downregulates Laminin α5 Expression in Tumor Endothelial Cells via the Inhibition of Nuclear Factor Kappa B Signaling

Carmona-Rodríguez

Martínez-Rey

Martín-González

et al. 2022

Cancers

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The balance between laminin isoforms containing the α5 or the α4 chain in the endothelial basement membrane determines the site of leukocyte diapedesis under inflammatory conditions. Extracellular superoxide dismutase (SOD3) induces laminin α4 expression in tumor blood vessels, which is associated with enhanced intratumor T cell infiltration in primary human cancers. We show now that SOD3 overexpression in neoplastic and endothelial cells (ECs) reduces laminin α5 in tumor blood vessels. SOD3 represses the laminin α5 gene (LAMA5), but LAMA5 expression is not changed in SOD1-overexpressing cells. Transcriptomic analyses revealed SOD3 overexpression to change the transcription of 1682 genes in ECs, with the canonical and non-canonical NF-κB pathways as the major SOD3 targets. Indeed, SOD3 reduced the transcription of well-known NF-κB target genes as well as NF-κB-driven promoter activity in ECs stimulated with tumor necrosis factor (TNF)-α, an NF-κB signaling inducer. SOD3 inhibited the phosphorylation and degradation of IκBα (nuclear factor of the kappa light polypeptide gene enhancer in B-cells inhibitor alpha), an NF-κB inhibitor. Finally, TNF-α was found to be a transcriptional activator of LAMA5 but not of LAMA4; LAMA5 induction was prevented by SOD3. In conclusion, SOD3 is a major regulator of laminin balance in the basement membrane of tumor ECs, with potential implications for immune cell infiltration into tumors.

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“…The expression of proteins found within the basement membrane network varies along the vascular beds. Laminin 411 and 511 are expressed in the endothelial basement membrane with low or patchy post-capillary venule expression of laminin 511 being preferential sites for leukocyte transmigration (Wu et al, 2009;Hallmann et al, 2020). Studies investigating neurodegenerative conditions, in conjunction with the use of transgenic animal models, have shown the important role that basement membrane proteins have in a functional and intact BBB (Thomsen et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

Tight Junctions of the Neurovascular Unit

Hudson

Campbell

2021

Front. Mol. Neurosci.

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The homeostatic balance of the brain and retina is maintained by the presence of the blood-brain and inner blood-retinal barrier (BBB/iBRB, respectively) which are highly specialized barriers. Endothelial cells forming the lining of these blood vessels are interconnected by the presence of tight junctions which form the BBB and iBRB. These tight junctions, formed of numerous interacting proteins, enable the entry of molecules into neural tissues while restricting the entry of harmful material such as anaphylatoxins, bacteria and viruses. If the tight junction complex becomes dysregulated due to changes in expression levels of one or more of the components, this can have detrimental effects leading to brain and retinal pathology.

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The role of basement membrane laminins in vascular function

Cited by 28 publications

References 59 publications

A guide to the composition and functions of the extracellular matrix

A guide to the composition and functions of the extracellular matrix

Superoxide Dismutase-3 Downregulates Laminin α5 Expression in Tumor Endothelial Cells via the Inhibition of Nuclear Factor Kappa B Signaling

Tight Junctions of the Neurovascular Unit

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