keyword
https://read.qxmd.com/read/38129319/ramipril-therapy-in-integrin-%C3%AE-1-null-autosomal-recessive-alport-mice-triples-lifespan-mechanistic-clues-from-rna-seq-analysis
#1
JOURNAL ARTICLE
Jacob Madison, Kevin Wilhelm, Daniel T Meehan, Michael Anne Gratton, Denise Vosik, Gina Samuelson, Megan Ott, John Fascianella, Noa Nelson, Dominic Cosgrove
The standard of care for patients with Alport syndrome (AS) is angiotensin-converting enzyme (ACE) inhibitors. In autosomal recessive Alport (ARAS) mice, ACE inhibitors double lifespan. We previously showed that deletion of Itga1 in Alport mice [double-knockout (DKO) mice] increased lifespan by 50%. This effect seemed dependent on the prevention of laminin 211-mediated podocyte injury. Here, we treated DKO mice with vehicle or ramipril starting at 4 weeks of age. Proteinuria and glomerular filtration rates were measured at 5-week intervals...
March 2024: Journal of Pathology
https://read.qxmd.com/read/37021539/vemurafenib-partially-ameliorates-muscle-histopathology-but-does-not-improve-muscle-function-in-a-mouse-model-of-lama2-cmd
#2
JOURNAL ARTICLE
Ariany Oliveira-Santos, Marisela Dagda, Jennifer Wittmann, Robert Smalley, Dean J Burkin
Laminin-α2-related Congenital Muscular Dystrophy (LAMA2-CMD) is a neuromuscular disease affecting around 1-9/1,000,000 children. LAMA2-CMD is caused by mutations in the LAMA2 gene resulting in the loss of laminin-211/221 heterotrimers in skeletal muscle. LAMA2-CMD patients exhibit severe hypotonia and progressive muscle weakness. Currently, there is no effective treatment for LAMA2-CMD and patients die prematurely. The loss of laminin-α2 results in muscle degeneration, defective muscle repair, and dysregulation of multiple signaling pathways...
April 6, 2023: Disease Models & Mechanisms
https://read.qxmd.com/read/36939258/preparation-of-3d-decellularized-matrices-from-fetal-mouse-skeletal-muscle-for-cell-culture
#3
JOURNAL ARTICLE
Pedro Gameiro Dos Santos, Ana Rita Soares, Sólveig Thorsteinsdóttir, Gabriela Rodrigues
The extracellular matrix (ECM) plays a crucial role in providing structural support for cells and conveying signals that are important for various cellular processes. Two-dimensional (2D) cell culture models oversimplify the complex interactions between cells and the ECM, as the lack of a complete three-dimensional (3D) support can alter cell behavior, making them inadequate for understanding in vivo processes. Deficiencies in ECM composition and cell-ECM interactions are important contributors to a variety of different diseases...
March 3, 2023: Journal of Visualized Experiments: JoVE
https://read.qxmd.com/read/36709920/aav-based-gene-therapy-prevents-and-halts-the-progression-of-dilated-cardiomyopathy-in-a-mouse-model-of-phosphoglucomutase-i-deficiency-pgm1-cdg
#4
JOURNAL ARTICLE
B Balakrishnan, R Altassan, R Budhraja, W Liou, A Lupo, S Bryant, A Mankouski, S Radenkovic, G Preston, A Pandey, S Boudina, T Kozicz, E Morava, K Lai
PGM1 deficiency is recognized as the third most common N-linked Congenital Disorders of Glycosylation (CDG) in humans. Affected individuals present with liver, musculoskeletal, endocrine, and coagulation symptoms; however, the most life-threatening complication is the early onset of dilated cardiomyopathy (DCM). Recently, we discovered that oral D-galactose supplementation improved liver disease, endocrine and coagulation abnormalities, but does not alleviate the fatal cardiomyopathy and the associated myopathy...
January 26, 2023: Translational Research: the Journal of Laboratory and Clinical Medicine
https://read.qxmd.com/read/36373293/lama2-related-muscular-dystrophy-the-importance-of-accurate-phenotyping-and-brain-imaging-in-the-diagnosis-of-lgmd
#5
JOURNAL ARTICLE
Tanya Stojkovic, Marion Masingue, Corinne Métay, Norma B Romero, Bruno Eymard, Rabah Ben Yaou, Laetitia Rialland, Séverine Drunat, Corine Gartioux, Isabelle Nelson, Valérie Allamand, Gisèle Bonne, Rocio Nur Villar-Quiles
We report three siblings from a non-consanguineous family presenting a with contractural limb-girdle phenotype with intrafamilial variability. Muscle MRI showed posterior thigh and quadriceps involvement with a sandwich-like sign. Whole-exome sequencing identified two compound heterozygous missense TTN variants and one heterozygous LAMA2 variant. Brain MRI performed because of concentration difficulties in one of the siblings evidenced white-matter abnormalities, subsequently found in the others. The genetic analysis was re-oriented, revealing a novel pathogenic intronic LAMA2 variant which confirmed the LAMA2-RD diagnosis...
November 11, 2022: Journal of Neuromuscular Diseases
https://read.qxmd.com/read/35924034/a-rare-case-of-arrhythmogenic-right-ventricular-cardiomyopathy-associated-with-lama2-mutation-a-case-report-and-literature-review
#6
Yue Wang, Yibing Fang, Dan Zhang, Yifei Li, Shuhua Luo
Background: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a heritable heart muscle disorder that predominantly affects the right ventricle. Mutations in genes that encode components of desmosomes, the adhesive junctions that connect cardiomyocytes, are the predominant cause of ARVC. A case with novel heterozygous mutation in the LAMA2 gene is reported here. The protein encoded by LAMA2 gene is the α2 chain of laminin-211 protein, which establishes a stable relationship between the muscle fiber membrane and the extracellular matrix...
2022: Frontiers in Medicine
https://read.qxmd.com/read/35813217/the-n-terminus-of-adhesion-g-protein-coupled-receptor-gpr126-adgrg6-as-allosteric-force-integrator
#7
JOURNAL ARTICLE
Jakob Mitgau, Julius Franke, Camilla Schinner, Gabriele Stephan, Sandra Berndt, Dimitris G Placantonakis, Hermann Kalwa, Volker Spindler, Caroline Wilde, Ines Liebscher
The adhesion G protein-coupled receptor (aGPCR) GPR126/ADGRG6 plays an important role in several physiological functions, such as myelination or peripheral nerve repair. This renders the receptor an attractive pharmacological target. GPR126 is a mechano-sensor that translates the binding of extracellular matrix (ECM) molecules to its N terminus into a metabotropic intracellular signal. To date, the structural requirements and the character of the forces needed for this ECM-mediated receptor activation are largely unknown...
2022: Frontiers in Cell and Developmental Biology
https://read.qxmd.com/read/35607980/glomerular-basement-membrane-deposition-of-collagen-%C3%AE-1-iii-in-alport-glomeruli-by-mesangial-filopodia-injures-podocytes-via-aberrant-signaling-through-ddr1-and-integrin-%C3%AE-2%C3%AE-1
#8
JOURNAL ARTICLE
Jacob Madison, Kevin Wilhelm, Daniel T Meehan, Duane Delimont, Gina Samuelson, Dominic Cosgrove
In Alport mice, activation of the endothelin A receptor (ETA R) in mesangial cells results in sub-endothelial invasion of glomerular capillaries by mesangial filopodia. Filopodia deposit mesangial matrix in the glomerular basement membrane (GBM), including laminin 211 which activates NF-κB, resulting in induction of inflammatory cytokines. Herein we show that collagen α1(III) is also deposited in the GBM. Collagen α1(III) localized to the mesangium in wild-type mice and was found in both the mesangium and the GBM in Alport mice...
September 2022: Journal of Pathology
https://read.qxmd.com/read/35121993/astrocytic-laminin-211-drives-disseminated-breast-tumor-cell-dormancy-in-brain
#9
JOURNAL ARTICLE
Jinxiang Dai, Patrick J Cimino, Kenneth H Gouin, Candice A Grzelak, Alexander Barrett, Andrea R Lim, Annalyssa Long, Stephanie Weaver, Lindsey T Saldin, Aiyedun Uzamere, Vera Schulte, Nigel Clegg, Laura Pisarsky, David Lyden, Mina J Bissell, Simon Knott, Alana L Welm, Jason H Bielas, Kirk C Hansen, Frank Winkler, Eric C Holland, Cyrus M Ghajar
Although dormancy is thought to play a key role in the metastasis of breast tumor cells to the brain, our knowledge of the molecular mechanisms regulating disseminated tumor cell (DTC) dormancy in this organ is limited. Here using serial intravital imaging of dormant and metastatic triple-negative breast cancer lines, we identify escape from the single-cell or micrometastatic state as the rate-limiting step towards brain metastasis. We show that every DTC occupies a vascular niche, with quiescent DTCs residing on astrocyte endfeet...
January 2022: Nature Cancer
https://read.qxmd.com/read/34965967/laminin-isoforms-in-human-dental-pulp-lymphatic-vessels-express-laminin-332-and-schwann-cell-associated-laminin-211-modulates-cd163-expression-of-m2-like-macrophages
#10
JOURNAL ARTICLE
Nagako Yoshiba, Naoki Edanami, Naoto Ohkura, Tomoki Maekawa, Naoki Takahashi, Takahiro Tsuzuno, Takeyasu Maeda, Koichi Tabeta, Kenji Izumi, Yuichiro Noiri, Kunihiko Yoshiba
Laminin, a basement membrane heterotrimeric glycoprotein composed of α/β/γ subunits, has important tissue-specific functions in the control of cellular behavior. Our recent study showed the colocalization of CD163+ M2-like macrophages with Schwann cells in human dental pulp, leading us to hypothesize that the laminin isoform of Schwann cells is associated with CD163 expression. The present study investigated the distribution of laminin isoforms in human dental pulp and the underlying mechanisms that affect macrophage phenotypes...
December 29, 2021: ImmunoHorizons
https://read.qxmd.com/read/34559299/diagnostic-interest-of-whole-body-mri-in-early-and-late-onset-lama2-muscular-dystrophies-a-large-international-cohort
#11
JOURNAL ARTICLE
Susana Quijano-Roy, Jana Haberlova, Claudia Castiglioni, John Vissing, Francina Munell, François Rivier, Tanya Stojkovic, Edoardo Malfatti, Marta Gómez García de la Banda, Giorgio Tasca, Laura Costa Comellas, Audrey Benezit, Helge Amthor, Ivana Dabaj, Clara Gontijo Camelo, Pascal Laforêt, John Rendu, Norma B Romero, Eliana Cavassa, Fabiana Fattori, Christophe Beroud, Jana Zídková, Nicolas Leboucq, Nicoline Løkken, Ángel Sanchez-Montañez, Ximena Ortega, Martin Kynčl, Corinne Metay, David Gómez-Andrés, Robert Y Carlier
BACKGROUND: LAMA2-related muscular dystrophy (LAMA2-RD) encompasses a group of recessive muscular dystrophies caused by mutations in the LAMA2 gene, which codes for the alpha-2 chain of laminin-211 (merosin). Diagnosis is straightforward in the classic congenital presentation with no ambulation and complete merosin deficiency in muscle biopsy, but is far more difficult in milder ambulant individuals with partial merosin deficiency. OBJECTIVE: To investigate the diagnostic utility of muscle imaging in LAMA2-RD using whole-body magnetic resonance imaging (WBMRI)...
May 2022: Journal of Neurology
https://read.qxmd.com/read/33869655/micro-laminin-gene-therapy-can-function-as-an-inhibitor-of-muscle-disease-in-the-dy-w-mouse-model-of-mdc1a
#12
JOURNAL ARTICLE
Davin Packer, Paul T Martin
Gene replacement for laminin-α2-deficient congenital muscular dystrophy 1A (MDC1A) is currently not possible using a single adeno-associated virus (AAV) vector due to the large size of the LAMA2 gene. LAMA2 encodes laminin-α2, a subunit of the trimeric laminin-211 extracellular matrix (ECM) protein that is the predominant laminin expressed in skeletal muscle. LAMA2 expression stabilizes skeletal muscle, in part by binding membrane receptors via its five globular (G) domains. We created a small, AAV-deliverable, micro-laminin gene therapy that expresses these G1-5 domains, LAMA2(G1-5) , to test their therapeutic efficacy in the dyW mouse model for MDC1A...
June 11, 2021: Molecular Therapy. Methods & Clinical Development
https://read.qxmd.com/read/33760980/the-extracellular-matrix-complexity-of-idiopathic-epiretinal-membranes-and-the-bilaminar-arrangement-of-the-associated-internal-limiting-membrane-in-the-posterior-retina
#13
JOURNAL ARTICLE
Annalisa Altera, Gian Marco Tosi, Marì Regoli, Elena De Benedetto, Eugenio Bertelli
PURPOSE: To study the composition of the internal limiting membrane (ILM) of the retina, the extracellular matrix (ECM) of idiopathic epiretinal membranes (iERMs), and the relationships occurring between the two membranes. METHODS: Forty-six iERMs, 24 of them associated with the ILM, were collected and included in this study. The investigation has been carried out by immunofluorescence and confocal microscopy on glutaraldehyde- and osmium-fixed epon-embedded samples and on frozen samples...
September 2021: Graefe's Archive for Clinical and Experimental Ophthalmology
https://read.qxmd.com/read/33387942/essential-roles-of-the-dystrophin-glycoprotein-complex-in-different-cardiac-pathologies
#14
REVIEW
Isela C Valera, Amanda L Wacker, Hyun Seok Hwang, Christina Holmes, Orlando Laitano, Andrew P Landstrom, Michelle S Parvatiyar
The dystrophin-glycoprotein complex (DGC), situated at the sarcolemma dynamically remodels during cardiac disease. This review examines DGC remodeling as a common denominator in diseases affecting heart function and health. Dystrophin and the DGC serve as broad cytoskeletal integrators that are critical for maintaining stability of muscle membranes. The presence of pathogenic variants in genes encoding proteins of the DGC can cause absence of the protein and/or alterations in other complex members leading to muscular dystrophies...
March 2021: Advances in Medical Sciences
https://read.qxmd.com/read/32987775/whole-exome-sequencing-as-a-diagnostic-tool-for-unidentified-muscular-dystrophy-in-a-vietnamese-family
#15
Ngoc-Lan Nguyen, Can Thi Bich Ngoc, Chi Dung Vu, Thi Thu Huong Nguyen, Huy Hoang Nguyen
Muscular dystrophies are a group of heterogeneous clinical and genetic disorders. Two siblings presented with characteristics like muscular dystrophy, abnormal white matter, and elevated serum creatine kinase level. The high throughput of whole exome sequencing (WES) makes it an efficient tool for obtaining a precise diagnosis without the need for immunohistochemistry. WES was performed in the two siblings and their parents, followed by prioritization of variants and validation by Sanger sequencing. Very rare variants with moderate to high predicted impact in genes associated with neuromuscular disorders were selected...
September 24, 2020: Diagnostics
https://read.qxmd.com/read/32848593/lama2-related-dystrophies-clinical-phenotypes-disease-biomarkers-and-clinical-trial-readiness
#16
REVIEW
Anna Sarkozy, A Reghan Foley, Alberto A Zambon, Carsten G Bönnemann, Francesco Muntoni
Mutations in the LAMA2 gene affect the production of the α2 subunit of laminin-211 (= merosin) and result in either partial or complete laminin-211 deficiency. Complete merosin deficiency is typically associated with a more severe congenital muscular dystrophy (CMD), clinically manifested by hypotonia and weakness at birth, the development of contractures of large joints, and progressive respiratory involvement. Muscle atrophy and severe weakness typically prevent independent ambulation. Partial merosin deficiency is mostly manifested by later onset limb-girdle weakness and joint contractures so that independent ambulation is typically achieved...
2020: Frontiers in Molecular Neuroscience
https://read.qxmd.com/read/32742259/zebrafish-models-of-lama2-related-congenital-muscular-dystrophy-mdc1a
#17
JOURNAL ARTICLE
Lacramioara Fabian, James J Dowling
LAMA2-related congenital muscular dystrophy (CMD; LAMA2-MD), also referred to as merosin deficient CMD (MDC1A), is a severe neonatal onset muscle disease caused by recessive mutations in the LAMA2 gene. LAMA2 encodes laminin α2, a subunit of the extracellular matrix (ECM) oligomer laminin 211. There are currently no treatments for MDC1A, and there is an incomplete understanding of disease pathogenesis. Zebrafish, due to their high degree of genetic conservation with humans, large clutch sizes, rapid development, and optical clarity, have emerged as an excellent model system for studying rare Mendelian diseases...
2020: Frontiers in Molecular Neuroscience
https://read.qxmd.com/read/32592615/the-laminin-211-derived-ppfegciwn-motif-accelerates-wound-reepithelialization-and-increases-phospho-fak-tyr397-and-rac1-gtp-levels-in-a-rat-excisional-wound-splinting-model
#18
JOURNAL ARTICLE
Seung Bin Jo, Cho Yeon Park, Hyun Ki Kang, Sung Youn Jung, Byung-Moo Min
We previously reported that the PPFEGCIWN motif (Ln2-LG3-P2-DN3), residues 2678-2686 of the human laminin α2 chain, promotes cell attachment of normal human epidermal keratinocytes (NHEKs) and dermal fibroblasts (NHDFs); however, its in vivo effects on cutaneous wound healing have not yet been examined. In this study, we sought to determine whether Ln2-LG3-P2-DN3 could promote full-thickness cutaneous wound healing by accelerating wound reepithelialization and wound closure in vivo. Ln2-LG3-P2-DN3 had significantly higher cell attachment and spreading activities than vehicle or scrambled peptide control in both NHEKs and NHDFs in vitro...
August 2020: Journal of Tissue Engineering and Regenerative Medicine
https://read.qxmd.com/read/32523512/impaired-regeneration-in-dystrophic-muscle-new-target-for-therapy
#19
JOURNAL ARTICLE
Nurit Yanay, Malcolm Rabie, Yoram Nevo
Muscle stem cells (MuSCs), known as satellite cells (SCs) have an incredible ability to regenerate, which enables the maintenance and growth of muscle tissue. In response to damaging stimuli, SCs are activated, proliferate, differentiate, and fuse to repair or generate a new muscle fiber. However, dystrophic muscles are characterized by poor muscle regeneration along with chronic inflammation and fibrosis. Indications for SC involvement in muscular dystrophy pathologies are accumulating, but their contribution to muscle pathophysiology is not precisely understood...
2020: Frontiers in Molecular Neuroscience
https://read.qxmd.com/read/32498713/human-laminin-111-and-laminin-211-protein-therapy-prevents-muscle-disease-progression-in-an-immunodeficient-mouse-model-of-lama2-cmd
#20
JOURNAL ARTICLE
Pamela Barraza-Flores, Hailey J Hermann, Christina R Bates, Tyler G Allen, Timothy T Grunert, Dean J Burkin
BACKGROUND: Laminin-α2-related congenital muscular dystrophy (LAMA2-CMD) is a devastating genetic disease caused by mutations in the LAMA2 gene. These mutations result in progressive muscle wasting and inflammation leading to delayed milestones, and reduced lifespan in affected patients. There is currently no cure or treatment for LAMA2-CMD. Preclinical studies have demonstrated that mouse laminin-111 can serve as an effective protein replacement therapy in a mouse model of LAMA2-CMD...
June 4, 2020: Skeletal Muscle
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