Obesity and neuroinflammatory phenotype in mice lacking endothelial megalin

Antequera, Desireé; Tavares, Eva; Pascual, Consuelo; Maldonado, Rosário; Camins, Antoni; Carro, Eva

doi:10.1186/s12974-017-0800-2

Cited by 26 publications

(25 citation statements)

References 45 publications

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“…Epiblastspecific inactivation of LRP2 via the MORE-cre results in a very similar phenotype clearly indicating the necessity of LRP2 in the embryonic tissues [30]. Mice lacking LRP2 in the brain microvessel endothelial cells present with cortical neurodegeneration and exhibit mild obesity and elevated leptin and insulin concentration further underlying the contribution of LRP2 in both metabolic and neurodegenerative diseases in the adult [28,33].…”

Section: Animal Models Of Lrp2 Inactivationmentioning

confidence: 90%

“…LRP2 ligands such as transthyretin, albumin, insulin, leptin or angiotensin II are implicated in HM, diabetes, obesity, hypertension and other pathological conditions which may affect both renal function and retinal health. With the exception of the renal effects of LRP2 dysfunction which have been extensively studied, the pathological mechanisms that relate LRP2 to other systems are not exactly defined [25][26][27][28].…”

Section: Lrp2mentioning

confidence: 99%

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LRP2 A Myopic Hotspot between Environment and Genetics

Kozyraki¹

2017

AOVS

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Myopia is typically due to the excessive growth of the eye resulting in blurred vision of distant objects. High myopia (HM) and its associated pathologies, i.e glaucoma, retinal detachments or myopic retinopathy are important causes of vision loss especially in young adults and their incidence is constantly on the rise. The mechanisms that regulate myopic eye growth are poorly understood but inherited, environmental and behavioral factors may contribute to the development of HM. HM is a cardinal feature of the Donnai-Barrow syndrome (DBS), a rare autosomal recessive condition combining facial dysmorphology, sensorineural hearing loss and proteinuria. DBS is caused by mutations in LRP2 encoding the low density lipoprotein receptor-related protein 2 (LRP2), a large endocytic receptor strongly expressed in the ocular epithelia and involved in the handling of various molecules including retinal, transthyretin, leptin or vitamin D. The ocular manifestations of DBS patients or mice lacking LRP2 specifically in the eye include excessively enlarged globes, increased axial length, retinal degeneration and detachments and normal intraocular pressure. Impaired formation of the endocytic apparatus is a common feature in the renal epithelia of DBS patients and the retinal pigment epithelium of the LRP2-deficient eyes suggesting that impaired transport or clearance of LRP2 ligands in the ocular tissues may be involved in myopia induction and progression. In this review we summarize current knowledge on myopia development and propose that modulating endocytosis of LRP2 and its ligands in the ocular tissues may be considered to prevent or control HM and its associated complications.

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Section: Animal Models Of Lrp2 Inactivationmentioning

confidence: 90%

Section: Lrp2mentioning

confidence: 99%

LRP2 A Myopic Hotspot between Environment and Genetics

Kozyraki¹

2017

AOVS

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“…It is a large membrane glycoprotein that belongs in the LDLR family. It is expressed on the apical membrane of several epithelial cells such as kidney proximal tubule cells, lung, thyroid, gallbladder, and neuroepithelium, as well as steroid-responsive tissues such as epididymis, prostate, ovaries, and uterus (156,157). The cytoplasmic domain is small and has been suggested to regulate its endocytic activities (158).…”

Section: Consensus Member Nomenclaturementioning

confidence: 99%

“…The cytoplasmic domain is small and has been suggested to regulate its endocytic activities (158). SR-L2 is expressed at the blood brain barrier where it binds and internalizes a variety of ligands such as leptin, insulin, and amyloid b peptide (157). Mice that lacked megalin/SR-L2 in brain endothelial cells exhibited neurodegeneration and neuroinflammation, as well as obesity (157).…”

Section: Consensus Member Nomenclaturementioning

confidence: 99%

“…SR-L2 is expressed at the blood brain barrier where it binds and internalizes a variety of ligands such as leptin, insulin, and amyloid b peptide (157). Mice that lacked megalin/SR-L2 in brain endothelial cells exhibited neurodegeneration and neuroinflammation, as well as obesity (157). Evidence has also been demonstrated for the role of peroxisome proliferator-activated receptors (termed PPARs) in regulating the expression of SR-L2 (158).…”

Section: Consensus Member Nomenclaturementioning

confidence: 99%

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A Consensus Definitive Classification of Scavenger Receptors and Their Roles in Health and Disease

PrabhuDas

Baldwin²,

Bollyky

et al. 2017

The Journal of Immunology

266

193

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Scavenger receptors constitute a large family of proteins that are structurally diverse and participate in a wide range of biological functions. These receptors are expressed predominantly by myeloid cells and recognize a diverse variety of ligands including endogenous and modified host-derived molecules and microbial pathogens. There are currently eight classes of scavenger receptors, many of which have multiple names, leading to inconsistencies and confusion in the literature. To address this problem, a workshop was organized by the United States National Institute of Allergy and Infectious Diseases, National Institutes of Health, to help develop a clear definition of scavenger receptors and a standardized nomenclature based on that definition. Fifteen experts in the scavenger receptor field attended the workshop and, after extensive discussion, reached a consensus regarding the definition of scavenger receptors and a proposed scavenger receptor nomenclature. Scavenger receptors were defined as cell surface receptors that typically bind multiple ligands and promote the removal of nonself or altered-self targets. They often function by mechanisms that include endocytosis, phagocytosis, adhesion, and signaling that ultimately lead to the elimination of degraded or harmful substances. Based on this definition, nomenclature and classification of these receptors into 10 classes were proposed. This classification was discussed at three national meetings and input from participants at these meetings was requested. The following manuscript is a consensus statement that combines the recommendations of the initial workshop and incorporates the input received from the participants at the three national meetings.

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