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https://www.readbyqxmd.com/read/29693448/three-dimensional-in-vitro-models-answer-the-right-questions-in-adpkd-cystogenesis
#1
Eryn E Dixon, Owen M Woodward
Novel technologies, new understanding of the basement membrane composition, and better comprehension of the embryonic development of the mammalian kidney have led to explosive growth in the use of three dimensional (3D) in vitro models to study a range of human disease pathologies(6, 35). The development of these effective model systems represents a new tool to study the progressive cystogenesis of autosomal dominant polycystic kidney disease (ADPKD). ADPKD is a prevalent and complex monogenetic disease, characterized by the pathological formation of fluid fill cysts in renal tissue(17, 40)...
April 25, 2018: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29689364/reversible-renal-glomerular-dysfunction-in-guinea-pigs-exposed-to-glutaraldehyde-polymerized-cell-free-hemoglobin
#2
Xiaoyuan Zhang, Matthew C Williams, Otgonchimeg Rentsendorj, Felice D'Agnillo
Chemically modified hemoglobin (Hb)-based oxygen carriers are promising oxygen replacement therapeutics however their potential renal effects are not fully understood. Using a guinea pig exchange transfusion model, we examined the effects of glutaraldehyde-polymerized bovine hemoglobin (HbG) on the permeability and integrity of the glomerular filtration barrier (GFB), which is comprised of podocytes, fenestrated endothelium, and the glomerular basement membrane. HbG induced marked proteinuria characterized in part by the loss of high molecular weight proteins, including albumin, immunoglobulin, and transferrin, at 4 and 12 hours post-infusion that resolved by 72 hours...
April 21, 2018: Toxicology
https://www.readbyqxmd.com/read/29686536/targeted-delivery-of-immuno-rnase-may-improve-cancer-therapy
#3
Miaonan Sun, Liankun Sun, Dejun Sun, Chunmei Zhang, Mei Li
Background: Immunotoxins are typical therapeutic drugs that can target cancer cells. They exploit the affinity of specific monoclonal antibodies or ligands to cancer cells to deliver a conjugated protein toxin to target sites, thus, attacking the cancer cells. Methods: The immuno-RNase, Onc-V3, showed the stability of Onc-V3 in the blood stream. Flow cytometry showed that apoptosis occurred in the HO-8910PM cells when treated with Onc-V3. Under the confocal microscope, the green fluorescent, FITC-Onc-V3, were located in the cytoplasm, suggesting that Onc-V3 had a function in the cytoplasm of cancer cells...
2018: Cancer Cell International
https://www.readbyqxmd.com/read/29681159/bullous-pemphigoid-a-10-year-study-of-discordant-results-on-direct-immunofluorescence
#4
Jessica G Fudge, Richard I Crawford
BACKGROUND: Bullous pemphigoid (BP) is the most common subepidermal autoimmune disorder characterized by tense bullae. It is associated with circulating autoantibodies against BP antigen-1 and BP antigen-2. Diagnosis is based upon clinical, histopathologic, and immunopathologic examination. Direct immunofluorescence (DIF) of perilesional skin highlights C3 with or without IgG in a linear pattern along the basement membrane. OBJECTIVES: We hypothesized that repeat biopsies may be required for a definitive DIF diagnosis of BP, as initial DIF evaluation may result in a false-negative result...
April 1, 2018: Journal of Cutaneous Medicine and Surgery
https://www.readbyqxmd.com/read/29678816/four-specific-ig-domains-in-unc-52-perlecan-function-with-nid-1-nidogen-during-dendrite-morphogenesis-in-caenorhabditis-elegans
#5
Kevin Celestrin, Carlos Díaz-Balzac, Leo T H Tang, Brian D Ackley, Hannes E Bülow
The extracellular matrix is essential for various aspects of nervous system patterning. For example, sensory dendrites in flies, worms and fish have been shown to rely on coordinated interactions of tissues with extracellular matrix proteins. Here we show that the conserved basement membrane protein UNC-52/Perlecan is required for establishing the correct number of the highly ordered dendritic trees in the somatosensory neuron PVD in Caenorhabditis elegans. This function of UNC-52/Perlecan is dependent on four conserved immunoglobulin domains, but independent of the known functions of UNC-52/Perlecan in mediating muscle-skin attachment...
April 20, 2018: Development
https://www.readbyqxmd.com/read/29678354/actin-dynamics-at-focal-adhesions-a-common-endpoint-and-putative-therapeutic-target-for-proteinuric-kidney-diseases
#6
REVIEW
Sanja Sever, Mario Schiffer
Proteinuria encompasses diverse causes including both genetic diseases and acquired forms such as diabetic and hypertensive nephropathy. The basis of proteinuria is a disturbance in size selectivity of the glomerular filtration barrier, which largely depends on the podocyte: a terminally differentiated epithelial cell type covering the outer surface of the glomerulus. Compromised podocyte structure is one of the earliest signs of glomerular injury. The phenotype of diverse animal models and podocyte cell culture firmly established the essential role of the actin cytoskeleton in maintaining functional podocyte structure...
April 17, 2018: Kidney International
https://www.readbyqxmd.com/read/29677463/a-role-for-collagen-iv-in-cardiovascular-disease
#7
Lasse Bach Steffensen, Lars M Rasmussen
Over the past decade, studies have repeatedly found single nucleotide polymorphisms located in the COL4A1 and COL4A2 genes to be associated with cardiovascular disease (CVD), and the 13q34 locus harboring these genes is one of approximately 160 genome-wide significant risk loci for coronary artery disease. COL4A1 and COL4A2 encode the ⍺1- and ⍺2-chains of collagen IV, a major component of basement membranes in various tissues including arteries. In spite of the growing body of evidence indicating a role for collagen IV in CVD, remarkably few studies aim at directly investigating such a role...
April 20, 2018: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/29673969/rgd-cadherins-and-%C3%AE-2%C3%AE-1-integrin-in-cancer-metastasis-a-dangerous-liaison
#8
REVIEW
J Ignacio Casal, Rubén A Bartolomé
We propose a new cadherin family classification comprising epithelial cadherins (cadherin 17 [CDH17], cadherin 16, VE-cadherin, cadherin 6 and cadherin 20) containing RGD motifs within their sequences. Expression of some RGD cadherins is associated with aggressive forms of cancer during the late stages of metastasis, and CDH17 and VE-cadherin have emerged as critical actors in cancer metastasis. After binding to α2β1 integrin, these cadherins promote integrin β1 activation, and thereby cell adhesion, invasion and proliferation, in liver and lung metastasis...
April 16, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29673759/alport-syndrome-and-pierson-syndrome-diseases-of-the-glomerular-basement-membrane
#9
REVIEW
Steven D Funk, Meei-Hua Lin, Jeffrey H Miner
The glomerular basement membrane (GBM) is an important component of the kidney's glomerular filtration barrier. Like all basement membranes, the GBM contains type IV collagen, laminin, nidogen, and heparan sulfate proteoglycan. It is flanked by the podocytes and glomerular endothelial cells that both synthesize it and adhere to it. Mutations that affect the GBM's collagen α3α4α5(IV) components cause Alport syndrome (kidney disease with variable ear and eye defects) and its variants, including thin basement membrane nephropathy...
April 16, 2018: Matrix Biology: Journal of the International Society for Matrix Biology
https://www.readbyqxmd.com/read/29672603/solo-a-rhoa-targeting-guanine-nucleotide-exchange-factor-is-critical-for-hemidesmosome-formation-and-acinar-development-in-epithelial-cells
#10
Sachiko Fujiwara, Tsubasa S Matsui, Kazumasa Ohashi, Shinji Deguchi, Kensaku Mizuno
Cell-substrate adhesions are essential for various physiological processes, including embryonic development and maintenance of organ functions. Hemidesmosomes (HDs) are multiprotein complexes that attach epithelial cells to the basement membrane. Formation and remodeling of HDs are dependent on the surrounding mechanical environment; however, the upstream signaling mechanisms are not well understood. We recently reported that Solo (also known as ARHGEF40), a guanine nucleotide exchange factor targeting RhoA, binds to keratin8/18 (K8/K18) intermediate filaments, and that their interaction is important for force-induced actin and keratin cytoskeletal reorganization...
2018: PloS One
https://www.readbyqxmd.com/read/29669314/three-novel-heterozygous-col4a4-mutations-result-in-three-different-collagen-type-iv-kidney-disease-phenotypes
#11
Ang Li, Er-Zhi Gao, Ying-Xia Cui, Jian-Hong Liu, Xing Lv, Xiu-Xiu Wei, Xin-Yi Xia, Chun-Lin Gao, Feng-Xia Liu, Zheng-Kun Xia, Asan, Zhi-Hong Liu, Xiao-Jun Li
Thin basement membrane nephropathy (TBMN), autosomal dominant Alport syndrome (ADAS), and focal segmental glomerulosclerosis (FSGS) are kidney diseases that differ in clinical diagnosis, treatment, and prognosis. Nevertheless, they may result from the same causative genes. Here, we report 3 COL4A4 heterozygous mutations (p.Gly208Arg, p.Ser513Glufs*2, and p.Met1617Cysfs*39) that lead to 3 different collagen type IV kidney disease phenotypes, manifesting as TBMN, ADAS, and FSGS. Using bioinformatics analyses and pedigree verification, we show that these novel variants are pathogenetic and cosegregate with TBMN, ADAS, and FSGS...
2018: Cytogenetic and Genome Research
https://www.readbyqxmd.com/read/29663371/distribution-of-extracellular-matrix-molecules-in-human-uterine-tubes-during-the-menstrual-cycle-a-histological-and-immunohistochemical-analysis
#12
Carlos Godoy-Guzmán, Claudio Nuñez, Pedro Orihuela, Antonio Campos, Víctor Carriel
The uterine tube (UT) is an important and complex organ of the women's reproductive system. In general, the anatomy and basic histology of this organ are well-known. However, the composition and function of the extracellular matrix (ECM) of the UT is still poorly understood. The ECM is a complex supramolecular material produced by cells which is commonly restricted to the basement membrane and interstitial spaces. ECM molecules play not only a structural role, they are also important for cell growth, survival and differentiation in all tissues...
April 16, 2018: Journal of Anatomy
https://www.readbyqxmd.com/read/29656960/circulating-vascular-basement-membrane-fragments-are-associated-with-the-diameter-of-the-abdominal-aorta-and-their-expression-pattern-is-altered-in-aaa-tissue
#13
Mari Holsti, Anders Wanhainen, Christina Lundin, Martin Björck, Gustaf Tegler, Johan Svensson, Malin Sund
OBJECTIVE: Abdominal aortic aneurysm (AAA) is characterised by enhanced proteolytic activity, and extracellular matrix (ECM) remodelling in the vascular wall. Type IV and XVIII collagen/endostatin are structural proteins in vascular basement membrane (VBM), a specialised ECM structure. Here the association between plasma levels of these collagens with the aortic diameter and expansion rate is studied, and their expression in aortic tissue characterised. METHODS: This was a retrospective population based cohort study...
April 12, 2018: European Journal of Vascular and Endovascular Surgery
https://www.readbyqxmd.com/read/29656148/basement-membrane-mechanics-shape-development-lesson-from-the-fly
#14
REVIEW
William Ramos-Lewis, Andrea Page-McCaw
Basement membrane plays a foundational role in the structure and maintenance of many tissues throughout the animal kingdom. In addition to signaling to cells through cell-surface receptors, basement membrane directly influences the development and maintenance of organ shape via its mechanical properties. The mechanical properties of basement membrane are dictated by its composition, geometry, and crosslinking. Distinguishing between the ways the basement membrane influences morphology in vivo poses a major challenge...
April 12, 2018: Matrix Biology: Journal of the International Society for Matrix Biology
https://www.readbyqxmd.com/read/29653141/dual-mechanism-of-type-vii-collagen-transfer-by-bone-marrow-mesenchymal-stem-cell-extracellular-vesicles-to-recessive-dystrophic-epidermolysis-bullosa-fibroblasts
#15
Jeffrey McBride, Luis Rodriguez-Menocal, Ambar Candanedo, Wellington Guzman, Marta Garcia-Contreras, Evangelos Badiavas
Recessive dystrophic epidermolysis bullosa (RDEB) is a severe blistering disease resulting from a lack of type VII collagen production. Recent clinical trials have shown efficacy of bone marrow-derived mesenchymal stem cells (BM-MSCs) in the treatment of epidermolysis bullosa, including improved basement membrane restructuring and cutaneous wound healing. The mechanism as to how type VII collagen is transferred from donor stem cell to recipient RDEB cells has not been defined. Here, we submit the model that BM-MSC-derived extracellular vesicles serve at least two roles: 1) to help transport type VII collagen within the extracellular space; and 2) to feed RDEB fibroblasts with messenger RNA that codes for type VII collagen, resulting in COL7A1 translation and synthesis of type VII collagen alpha chain proteins by RDEB fibroblasts...
April 10, 2018: Biochimie
https://www.readbyqxmd.com/read/29651426/4-hydroxy-2-nonenal-alkylated-and-peroxynitrite-nitrated-proteins-localize-to-the-fused-mitochondria-in-malpighian-epithelial-cells-of-type-iv-collagen-drosophila-mutants
#16
András A Kiss, Nikoletta Popovics, Zsolt Boldogkői, Katalin Csiszár, Mátyás Mink
Background . Human type IV collagenopathy is associated with mutations within the COL4A1 and to a less extent the COL4A2 genes. The proteins encoded by these genes form heterotrimers and are the highest molar ratio components of the ubiquitous basement membrane. The clinical manifestations of the COL4A1/A2 mutations are systemic affecting many tissues and organs among these kidneys. In order to uncover the cellular and biochemical alterations associated with aberrant type IV collagen, we have explored the phenotype of the Malpighian tubules, the secretory organ and insect kidney model, in col4a1 collagen gene mutants of the fruit fly Drosophila melanogaster ...
2018: BioMed Research International
https://www.readbyqxmd.com/read/29649546/pulmonary-immunity-and-extracellular-matrix-interactions
#17
REVIEW
David N O'Dwyer, Stephen J Gurczynski, Bethany B Moore
The lung harbors a complex immune system composed of both innate and adaptive immune cells. Recognition of infection and injury by receptors on lung innate immune cells is crucial for generation of antigen-specific responses by adaptive immune cells. The extracellular matrix of the lung, comprising the interstitium and basement membrane, plays a key role in the regulation of these immune systems. The matrix consists of several hundred assembled proteins that interact to form a bioactive scaffold. This template, modified by enzymes, acts to facilitate cell function and differentiation and changes dynamically with age and lung disease...
April 9, 2018: Matrix Biology: Journal of the International Society for Matrix Biology
https://www.readbyqxmd.com/read/29649307/bilateral-carotid-artery-stenosis-causes-unexpected-early-changes-in-brain-extracellular-matrix-and-blood-brain-barrier-integrity-in-mice
#18
Jill M Roberts, Michael E Maniskas, Gregory J Bix
Bilateral carotid artery stenosis (BCAS) is one experimental model of vascular dementia thought to preferentially impact brain white matter. Indeed, few studies report hippocampal and cortical pathology prior to 30 days post-stenosis; though it is unclear whether those studies examined regions outside the white matter. Since changes in the blood-brain barrier (BBB) permeability precede more overt brain pathology in various diseases, we hypothesized that changes within the BBB and/or BBB-associated extracellular matrix (ECM) could occur earlier after BCAS in the hippocampus, cortex and striatum and be a precursor of longer term pathology...
2018: PloS One
https://www.readbyqxmd.com/read/29644905/histopathology-in-chronic-rhinosinusitis-varies-with-sinus-culture
#19
Ashley L Heilingoetter, Bobby Tajudeen, Hannah N Kuhar, Paolo Gattuso, Ritu Ghai, Mahboobeh Mahdavinia, Pete S Batra
Background Structured histopathology reporting facilitates better understanding of the underlying pathophysiologic mechanisms of chronic rhinosinusitis. The microbiology of chronic rhinosinusitis has been studied extensively; however, distinct histopathologic changes associated with bacteria isolated in chronic rhinosinusitis are largely unknown. Objective The goal of this study is to better understand the relationship between culturable bacteria and histopathology in chronic rhinosinusitis. Methods A structured histopathology report was utilized to analyze sinus tissue removed during functional endoscopic sinus surgery in a group of patients with chronic rhinosinusitis refractory to medical therapy...
March 2018: American Journal of Rhinology & Allergy
https://www.readbyqxmd.com/read/29644110/ameliorative-effect-of-vitamin-b12-on-seminiferous-epithelium-of-cimetidine-treated-rats-a-histopathological-immunohistochemical-and-ultrastructural-study
#20
Wael M Elsaed, Raouf Fekry Bedeer, Mohamed Ahmed Eladl
Cimetidine is an H2 receptor antagonist that has an antiandrogenic effect. It intervenes with the conversion of testosterone into estrogen in the Sertoli cells with accompanying testicular structural changes. In the present study, the microscopic and the ultrastructural changes induced by cimetidine and the effect of vitamin B12 as a protective agent on rat testes were studied. Immunoexpression of estrogen receptor β (ERβ) in testes was evaluated. Twenty-four adult male rats were divided into four groups: control, cimetidine-treated, vitamin B12 treated, and combined cimetidine and vitamin B12 treated...
March 2018: Anatomy & Cell Biology
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