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basement membrane

E Mammadova-Bach, T Rupp, C Spenlé, I Jivkov, P Shankaranarayanan, A Klein, L Pisarsky, A Méchine-Neuville, G Cremel, M Kedinger, O De Wever, N Ambartsumian, S Robine, E Pencreach, D Guenot, P Simon-Assmann, J G Goetz, G Orend, O Lefebvre
Tumor stroma remodeling is a key feature of malignant tumors and can promote cancer progression. Laminins are major constituents of basement membranes that physically separate the epithelium from the underlying stroma. By employing mouse models expressing high and low levels of the laminin α1 chain (LMα1), we highlighted its implication in a tumor-stroma crosstalk, thus leading to increased colon tumor incidence, angiogenesis and tumor growth. The underlying mechanism involves attraction of carcinoma-associated fibroblasts by LMα1, VEGFA expression triggered by the complex integrin α2β1-CXCR4 and binding of VEGFA to LM-111, which in turn promotes angiogenesis, tumor cell survival and proliferation...
June 15, 2018: Biology of the Cell
Aki Natsumi, Koji Sugawara, Makiko Yasumizu, Yukari Mizukami, Shigetoshi Sano, Akimichi Morita, Ralf Paus, Daisuke Tsuruta
Psoriasis is a complex chronic inflammatory skin disease characterized by epidermal thickening on the basis of increased keratinocyte proliferation and insufficient apoptosis. Laminins are important components of the basement membrane (BM) and impact on epidermal keratinocyte growth/apoptosis. Although several laminins are involved in the pathogenesis of psoriasis, it is still controversial about the expression patterns of laminin isoforms and which laminins are important in the development of psoriasis. Because laminin-511 and -332 are key BM components in human skin, and laminin-511 stimulates human hair follicle growth, we asked whether the BM zone in psoriasis shows any laminin-related abnormalities...
June 1, 2018: Journal of Histochemistry and Cytochemistry: Official Journal of the Histochemistry Society
Anita C Randolph, Satoshi Fukuda, Koji Ihara, Perenlei Enkhbaatar, Maria-Adelaide Micci
Only a handful of published reports exist today that describe neurological complications following smoke inhalation injury. In this study, we characterize acute pathophysiological changes in the brain of sheep exposed to smoke inhalation, with- and without third-degree skin burn that models the injuries sustained by human victims of fire accidents. Blood-brain barrier integrity and hemorrhage were analyzed throughout the brain using specific histological stains: Hematoxylin & Eosin, Luxol fast blue, Periodic acid-Schiff (PAS), and Martius, Scarlet and Blue (MSB)...
June 13, 2018: Shock
Shiki Takamura
Tissue-resident memory T cells (TRM cells) are a population of immune cells that reside in the lymphoid and non-lymphoid organs without recirculation through the blood. These important cells occupy and utilize unique anatomical and physiological niches that are distinct from those for other memory T cell populations, such as central memory T cells in the secondary lymphoid organs and effector memory T cells that circulate through the tissues. CD8+ TRM cells typically localize in the epithelial layers of barrier tissues where they are optimally positioned to act as sentinels to trigger antigen-specific protection against reinfection...
2018: Frontiers in Immunology
Mohammad M Faghih, M Keith Sharp
BACKGROUND: Transport of solutes has been observed in the spaces surrounding cerebral arteries and veins. Indeed, transport has been found in opposite directions in two different spaces around arteries. These findings have motivated hypotheses of bulk flow within these spaces. The glymphatic circulation hypothesis involves flow of cerebrospinal fluid from the cortical subarachnoid space to the parenchyma along the paraarterial (extramural, Virchow-Robin) space around arteries, and return flow to the cerebrospinal fluid (CSF) space via paravenous channels...
June 15, 2018: Fluids and Barriers of the CNS
Wenjin Yan, Jin Dai, Dongquan Shi, Xingquan Xu, Xiao Han, Zhihong Xu, Dongyang Chen, Huajiang Teng, Qing Jiang
Schwartz-Jampel syndrome type 1 (SJS1) is a rare autosomal recessive disease caused by mutations in the gene heparan sulfate proteoglycan 2 (HSPG2; also known as basement membrane‑specific heparin sulfate). In the present study, a 10‑year‑old female SJS1 proband from a Chinese family, who was diagnosed by X‑ray and physical examination, was recruited. The key clinical features of the patient with SJS1 included short stature, joint contractures, pigeon breast, and myotonia that led to progressive stiffness of the face and limbs; barely discernible kyphosis was also noted...
June 6, 2018: Molecular Medicine Reports
Lulin Huang, Yao Mao, Jiyun Yang, Yuanfeng Li, Yang Li, Zhenglin Yang
OBJECTIVES: USH2A encodes for usherin, a basement membrane protein in the inner ear and retina. USH2A can cause retinitis pigmentosa (RP) with or without hearing loss. The aim of this study was to detect USH2A mutations in a Chinese cohort of 75 small RP families and 10 Usher syndrome families. METHODS: We performed a direct Sanger sequencing analysis of the USH2A gene to identify mutations for this cohort. RESULTS: We identified a total of eight mutations in four of the 75 small RP families (5...
June 13, 2018: Eye
John K Brealey, John Cassidy, Jim Manavis
Microvascular injury is an important factor in renal allograft survival. Repeated episodes of endothelial injury from chronic antibody-mediated rejection typically manifest at the ultrastructural level as circumferential multilayering of remodeled glomerular basement membrane material and peritubular capillary basal lamina. In contrast to this typical pattern of microvascular injury, a renal transplantation case is presented in which focally dilated and multilayered segments of peritubular capillary basal lamina bearing lipid droplets were interspersed with ultrastructurally normal unilayered segments of basal lamina devoid of lipid droplets...
June 13, 2018: Ultrastructural Pathology
Xueyan Wang, Huajing Wan, Shuo Yang, Rong Zhou, Yong Liao, Fan Wang, Ximin Chen, Zhiling Wu
Objective The study aimed to investigate the role of high Krüppel-like factor 5 (KLF5) expression on the pathogenesis of congenital cystic adenomatoid malformation of the lungs (CCAML) in mice. Methods A mouse model of high KLF5 expression in the lungs was established. KLF5 expression and the pulmonary lumen diameter were examined by immunohistochemistry to determine a successful model. Basement membrane damage and activity of matrix metalloproteinase-9 (MMP-9) were examined. After an adenovirus carrying KLF5 gene transfection in lung adenocarcinoma (H441) was created, changes in expression and activity of MMP-9 were determined...
January 1, 2018: Journal of International Medical Research
Genki Hayashi, Cassandre Labelle-Dumais, Douglas B Gould
Collagen type IV alpha 1 (COL4A1) and alpha 2 (COL4A2) form heterotrimers that constitute a major component of nearly all basement membranes. COL4A1 and COL4A2 mutations cause a multisystem disorder that includes variable cerebrovascular and skeletal muscle manifestations. The pathogenicity of COL4A1 and COL4A2 mutations is generally attributed to impaired secretion into basement membranes. Sodium 4-phenylbutyrate (4PBA) is an FDA-approved drug that promotes mutant heterotrimer secretion in vitro and in vivo Here, we use different 4PBA treatment paradigms to define therapeutic parameters for preventing cerebrovascular and muscular pathologies in Col4a1 mutant mice...
June 12, 2018: Disease Models & Mechanisms
Gerd Geerling, Walter Lisch, David Finis
The corneal epithelium is the most important structure of the ocular optical system. Recurrent corneal erosions can result from inflammation, trauma, degeneration and dystrophies. Epithelial basement membrane dystrophy (EBMD), epithelial recurrent erosion dystrophy (ERED) and Francheschetti and Meesmann's epithelial corneal dystrophy (MECD) can all - besides other signs and symptoms - result in more or less frequent corneal erosions. The pathomechanisms involved however are different. In EBMD, corneal erosions are facultative and clinical signs are often subtle...
June 2018: Klinische Monatsblätter Für Augenheilkunde
André Vicente, Berit Byström, Mona Lindström, Ulf Stenevi, Fátima Pedrosa Domellöf
BACKGROUND: To study structural changes in naïve and surgically treated corneas of aniridia patients with advanced aniridia-related keratopathy (ARK). METHODS AND FINDINGS: Two naïve corneal buttons from patients with advanced ARK submitted to penetrating keratoplasty for the first time, one corneal button from an ARK patient that had undergone a keratolimbal allograft (KLAL), two corneal buttons from ARK patients who had previously undergone centered or decentered transplantation and were now retransplanted and two adult healthy donor control corneas were processed for immunohistochemistry...
2018: PloS One
Hua Wong, Jessica Prévoteau-Jonquet, Stéphanie Baud, Manuel Dauchez, Nicolas Belloy
The extracellular matrix (ECM) plays an important role in supporting tissues and organs. It even has a functional role in morphogenesis and differentiation by acting as a source of active molecules (matrikines). Many diseases are linked to dysfunction of ECM components and fragments or changes in their structures. As such it is a prime target for drugs. Because of technological limitations for observations at mesoscopic scales, the precise structural organisation of the ECM is not well-known, with sparse or fuzzy experimental observables...
June 11, 2018: Journal of Integrative Bioinformatics
Zivile D Békássy, Ann-Charlotte Kristoffersson, Johan Rebetz, Ramesh Tati, Anders I Olin, Diana Karpman
Certain kidney diseases are associated with complement activation although a renal triggering factor has not been identified. Here we demonstrated that renin, a kidney-specific enzyme, cleaves C3 into C3b and C3a, in a manner identical to the C3 convertase. Cleavage was specifically blocked by the renin inhibitor aliskiren. Renin-mediated C3 cleavage and its inhibition by aliskiren also occurred in serum. Generation of C3 cleavage products was demonstrated by immunoblotting, detecting the cleavage product C3b, by N-terminal sequencing of the cleavage product, and by ELISA for C3a release...
June 5, 2018: Kidney International
Srilatha Reddy Gantala, Mrudula Spurthi Kondapalli, Ramanjaneyulu Kummari, Chiranjeevi Padala, Mohini Aiyengar Tupurani, Keerthi Kupsal, Rajesh Kumar Galimudi, Kishore Kumar Gundapaneni, Kaushik Puranam, Nivas Shyamala, Swarnalatha Guditi, Ram Rapur, Surekha Rani Hanumanth
Type 2 Diabetic Nephropathy (DN) is a common multifactorial disorder. Degradation of glomerular basement membrane (GBM) by matrix metalloproteinases (MMPs) is a key event in the progression of renal disease. A functional polymorphism at position -1607 1G/2G, -1306 C/T and -1171 5A/6A has been shown to alter the transcriptional activity of MMP-1, MMP-2 and MMP-3 respectively, and also associated with several diseases contributing to inter-individual differences in susceptibility to type 2 DN. The study population consisted of 310 type 2 DN patients and 310 healthy controls...
June 5, 2018: Gene
Claudia Kühlbach, Sabrina da Luz, Frank Baganz, Volker C Hass, Margareta M Mueller
Metastatic dissemination of cancer cells is a very complex process. It includes the intravasation of cells into the metastatic pathways, their passive distribution within the blood or lymph flow, and their extravasation into the surrounding tissue. Crucial steps during extravasation are the adhesion of the tumor cells to the endothelium and their transendothelial migration. However, the molecular mechanisms that are underlying this process are still not fully understood. Novel three dimensional (3D) models for research on the metastatic cascade include the use of microfluidic devices...
May 23, 2018: Bioengineering
Olivier Gaudin, Vannina Seta, Marina Alexandre, Gérôme Bohelay, Françoise Aucouturier, Sabine Mignot-Grootenboer, Saskia Ingen-Housz-Oro, Céline Bernardeschi, Pierre Schneider, Benoît Mellottee, Frédéric Caux, Catherine Prost-Squarcioni
Mucous membrane pemphigoids (MMPs) and bullous pemphigoid (BP) are autoimmune bullous diseases that share physiopathological features: both can result from autoantibodies directed against BP180 or BP230 antigens. An association has been reported between BP and intake of gliptins, which are dipeptidyl peptidase-IV inhibitors used to treat type 2 diabetes mellitus. Clinical and immunological differences have been reported between gliptin-induced BPs and classical BPs: mucosal involvement, non-inflammatory lesions, and target BP180 epitopes other than the NC16A domain...
2018: Frontiers in Immunology
Wei Wu, Wei Hu, Wen-Bei Han, Ying-Lu Liu, Yue Tu, Hai-Ming Yang, Qi-Jun Fang, Mo-Yi Zhou, Zi-Yue Wan, Ren-Mao Tang, Hai-Tao Tang, Yi-Gang Wan
Huangkui capsule (HKC), a Chinese modern patent medicine extracted from Abelmoschus manihot (L.) medic, has been widely applied to clinical therapy in the early diabetic nephropathy (DN) patients. However, it remains elusive whether HKC can ameliorate the inchoate glomerular injuries in hyperglycemia. Recently the activation of phosphatidylinositol-3-kinase (PI3K)/serine-threonine kinase (Akt)/mammalian target of rapamycin (mTOR) signaling and its downstream regulator, 70-kDa ribosomal protein S6 kinase (p70S6K), play important roles in the early glomerular pathological changes of DN including glomerular hypertrophy, glomerular basement membrane (GBM) thickening and mild mesangial expansion...
2018: Frontiers in Pharmacology
Federica Moalli, Xenia Ficht, Philipp Germann, Mykhailo Vladymyrov, Bettina Stolp, Ingrid de Vries, Ruth Lyck, Jasmin Balmer, Amleto Fiocchi, Mario Kreutzfeldt, Doron Merkler, Matteo Iannacone, Akitaka Ariga, Michael H Stoffel, James Sharpe, Martin Bähler, Michael Sixt, Alba Diz-Muñoz, Jens V Stein
T cells are actively scanning pMHC-presenting cells in lymphoid organs and nonlymphoid tissues (NLTs) with divergent topologies and confinement. How the T cell actomyosin cytoskeleton facilitates this task in distinct environments is incompletely understood. Here, we show that lack of Myosin IXb (Myo9b), a negative regulator of the small GTPase Rho, led to increased Rho-GTP levels and cell surface stiffness in primary T cells. Nonetheless, intravital imaging revealed robust motility of Myo9b-/- CD8+ T cells in lymphoid tissue and similar expansion and differentiation during immune responses...
June 6, 2018: Journal of Experimental Medicine
Saptarshi Biswas, Jared Watters, Galina Bachay, Shweta Varshney, Dale D Hunter, Huaiyu Hu, William J Brunken
Proper arteriovenous morphogenesis is crucial for maintaining normal tissue perfusion. However, our understanding of how arterial morphogenesis is regulated in the CNS is incomplete. In this study, we asked whether vascular basement membrane (BM) laminins, specifically the γ3-containing isoforms, regulate retinal arterial morphogenesis. We provide evidence that Laminin-γ3 is deposited at both arterial and venous BMs during arteriogenesis. Vascular BM Laminin-γ3 bound dystroglycan (DG), a laminin receptor preferentially expressed by arterial endothelial cells (ECs) during arteriogenesis...
June 6, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
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