Endothelial basement membrane laminin 511 is essential for shear stress response

Russo, Jacopo Di; Luik, Anna-Liisa; Yousif, Lema F.; Budny, Sigmund; Oberleithner, Hans; Hofschröer, Verena; Klingauf, Juergen; Bavel, Ed; Bakker, Erik N. T. P.; Hellstrand, Per; Bhattachariya, Anirban; Albinsson, Sebastian; Pincet, Frédéric; Sorokin, Lydia

doi:10.15252/embj.201797000

Cited by 13 publications

(23 citation statements)

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“…Endothelial cells primarily produce laminin‐411 and ‐511 (Sixt et al ., ; Yousif et al ., ; Di Russo et al ., ). To investigate their roles in BBB integrity, various laminin loss‐of‐function mutants have been generated and studied.…”

Section: Functions Of Laminins and Their Receptorsmentioning

confidence: 97%

“…Astrocytes predominantly synthesize laminin‐211 (Hallmann et al ., ; Di Russo et al ., ; Hannocks et al ., ). Various laminin mutant mouse lines have been used to investigate its function in BBB integrity.…”

Section: Functions Of Laminins and Their Receptorsmentioning

confidence: 97%

“…Laminin‐γ1, the most common γ subunit, is widely expressed in the CNS. Its expression has been found in neural folds (Copp et al ., ), endoneurium/neuroectoderm (Gersdorff et al ., ; Copp et al ., ), BM and pia (Sixt et al ., ; Hallmann et al ., ; Yousif, Di Russo & Sorokin, ; Di Russo et al ., ; Hannocks et al ., ). Unlike laminin‐γ1 chain, restricted expression of laminin‐γ2 and ‐γ3 subunits are observed in the CNS.…”

Section: Expression Of Laminins and Their Receptors In The Cnsmentioning

confidence: 99%

“…For example, BMECs have less pinocytotic vesicles/fenestrations and express high levels of tight junction proteins at intercellular spaces (Kniesel & Wolburg, ; Bazzoni & Dejana, ), which reduce transcellular and paracellular permeability, respectively. Previous studies have shown that BMECs primarily express laminin‐411 and ‐511 (Sixt et al ., ; Yousif et al ., ; Di Russo et al ., ), which contribute to the formation of endothelial BM (Fig. ).…”

Section: Expression Of Laminins and Their Receptors In The Cnsmentioning

confidence: 99%

“…Mounting evidence shows that endothelial cells mainly express integrin‐α3β1 (Kikkawa et al ., ; Fujiwara et al ., ; Carlson et al ., ; Lei et al ., ; Di Russo et al ., ), ‐α6β1 (Kikkawa et al ., ; Fujiwara et al ., ; Carlson et al ., ; Lei et al ., ; Di Russo et al ., ) and ‐α6β4 (Kikkawa et al ., ) under normal conditions, although integrin‐α2 expression is also reported (Paulus et al ., ). Under pathological conditions, however, not only are the expression levels of these integrins altered, new integrin heterodimers, including αv‐integrins, are induced in endothelial cells (Friedlander et al ., ; Okada et al ., ; Abumiya et al ., ; Milner et al ., ).…”

Section: Expression Of Laminins and Their Receptors In The Cnsmentioning

confidence: 99%

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Laminins and their receptors in the CNS

Nirwane

Yao

2018

Biological Reviews

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Laminin, an extracellular matrix protein, is widely expressed in the central nervous system (CNS). By interacting with integrin and non-integrin receptors, laminin exerts a large variety of important functions in the CNS in both physiological and pathological conditions. Due to the existence of many laminin isoforms and their differential expression in various cell types in the CNS, the exact functions of each individual laminin molecule in CNS development and homeostasis remain largely unclear. In this review, we first briefly introduce the structure and biochemistry of laminins and their receptors. Next, the dynamic expression of laminins and their receptors in the CNS during both development and in adulthood is summarized in a cell-type-specific manner, which allows appreciation of their functional redundancy/compensation. Furthermore, we discuss the biological functions of laminins and their receptors in CNS development, blood-brain barrier (BBB) maintenance, neurodegeneration, stroke, and neuroinflammation. Last, key challenges and potential future research directions are summarized and discussed. Our goals are to provide a synthetic review to stimulate future studies and promote the formation of new ideas/hypotheses and new lines of research in this field.

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Section: Functions Of Laminins and Their Receptorsmentioning

confidence: 97%

Section: Functions Of Laminins and Their Receptorsmentioning

confidence: 97%

Section: Expression Of Laminins and Their Receptors In The Cnsmentioning

confidence: 99%

Section: Expression Of Laminins and Their Receptors In The Cnsmentioning

confidence: 99%

Section: Expression Of Laminins and Their Receptors In The Cnsmentioning

confidence: 99%

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Laminins and their receptors in the CNS

Nirwane

Yao

2018

Biological Reviews

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Intra-vessel heterogeneity establishes enhanced sites of macromolecular leakage downstream of laminin α5

et al. 2021

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Intra-vessel heterogeneity establishes enhanced sites of macromolecular leakage downstream of laminin a5 Graphical abstract Highlights d Intra-vessel heterogeneity produces sites of predetermined leakage d Predetermined sites of leakage are preserved between agonists and vascular beds d Low laminin a5 defines sites of predetermined leakage d Laminin a5 promotes junctional VE-cadherin and attenuates Y685 phosphorylation

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The molecular mechanism of mechanotransduction in vascular homeostasis and disease

Yamashiro

Yanagisawa

2020

Clinical Science

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Blood vessels are constantly exposed to mechanical stimuli such as shear stress due to flow and pulsatile stretch. The extracellular matrix maintains the structural integrity of the vessel wall and coordinates with a dynamic mechanical environment to provide cues to initiate intracellular signaling pathway(s), thereby changing cellular behaviors and functions. However, the precise role of matrix–cell interactions involved in mechanotransduction during vascular homeostasis and disease development remains to be fully determined. In this review, we introduce hemodynamics forces in blood vessels and the initial sensors of mechanical stimuli, including cell–cell junctional molecules, G-protein-coupled receptors (GPCRs), multiple ion channels, and a variety of small GTPases. We then highlight the molecular mechanotransduction events in the vessel wall triggered by laminar shear stress (LSS) and disturbed shear stress (DSS) on vascular endothelial cells (ECs), and cyclic stretch in ECs and vascular smooth muscle cells (SMCs)—both of which activate several key transcription factors. Finally, we provide a recent overview of matrix–cell interactions and mechanotransduction centered on fibronectin in ECs and thrombospondin-1 in SMCs. The results of this review suggest that abnormal mechanical cues or altered responses to mechanical stimuli in EC and SMCs serve as the molecular basis of vascular diseases such as atherosclerosis, hypertension and aortic aneurysms. Collecting evidence and advancing knowledge on the mechanotransduction in the vessel wall can lead to a new direction of therapeutic interventions for vascular diseases.

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Endothelial basement membrane laminin 511 is essential for shear stress response

Cited by 13 publications

References 1 publication

Laminins and their receptors in the CNS

Laminins and their receptors in the CNS

Intra-vessel heterogeneity establishes enhanced sites of macromolecular leakage downstream of laminin α5

The molecular mechanism of mechanotransduction in vascular homeostasis and disease

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