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Matrix Biology : Journal of the... Aug 2023During ageing, the glomerular and tubular basement membranes (BM) of the kidney undergo a progressive decline in function that is underpinned by histological changes,...
During ageing, the glomerular and tubular basement membranes (BM) of the kidney undergo a progressive decline in function that is underpinned by histological changes, including glomerulosclerosis and tubular interstitial fibrosis and atrophy. This BM-specific ageing is thought to result from damage accumulation to long-lived extracellular matrix (ECM) protein structures. Determining which BM proteins are susceptible to these structure-associated changes, and the possible mechanisms and downstream consequences, is critical to understand age-related kidney degeneration and to identify markers for therapeutic intervention. Peptide location fingerprinting (PLF) is an emerging proteomic mass spectrometry analysis technique capable of identifying ECM proteins with structure-associated differences that may occur by damage modifications in ageing. Here, we apply PLF as a bioinformatic screening tool to identify BM proteins with structure-associated differences between young and aged human glomerular and tubulointerstitial compartments. Several functional regions within key BM components displayed alterations in tryptic peptide yield, reflecting potential age-dependent shifts in molecular (e.g. laminin-binding regions in agrin) and cellular (e.g. integrin-binding regions in laminins 521 and 511) interactions, oxidation (e.g. collagen IV) and the fragmentation and release of matrikines (e.g. canstatin and endostatin from collagens IV and XVIII). Furthermore, we found that periostin and the collagen IV α2 chain exhibited structure-associated differences in ageing that were conserved between human kidney and previously analysed mouse lung, revealing BM components that harbour shared susceptibilities across species and organs.
Topics: Mice; Animals; Humans; Aged; Proteomics; Basement Membrane; Kidney; Extracellular Matrix Proteins; Collagen Type IV; Laminin; Kidney Diseases
PubMed: 37437747
DOI: 10.1016/j.matbio.2023.07.001 -
BMC Developmental Biology Nov 2010Initiation of the hair follicle placode and its subsequent growth, maturation and cycling in post-natal skin requires signaling interactions between epithelial cells and...
BACKGROUND
Initiation of the hair follicle placode and its subsequent growth, maturation and cycling in post-natal skin requires signaling interactions between epithelial cells and adjacent dermal cells and involves Shh signaling via the primary cilium. Previous reports have implicated laminins in hair follicle epithelial invagination.
RESULTS
Here we use a human BCC model system and mouse mutants to re-evaluate the role of laminin-511 in epithelial invagination in the skin. Blocking laminin 511 and 332 in BCCs maintains primary cilia and Shh signalling, but prevents invagination. Similarly, in laminin-511 and dermal beta-1 integrin mutants, dermal papilla development and primary cilia formation are normal. Dermal beta-1 integrin mutants have normal hair follicle development.
CONCLUSIONS
Our data provides support for a primary role of laminin-511 promoting hair follicle epithelial downgrowth without affecting dermal primary cilia and Shh target gene induction.
Topics: Animals; Biomarkers; Carcinoma, Basal Cell; Cell Adhesion Molecules; Hair Follicle; Hedgehog Proteins; Humans; Integrin beta1; Laminin; Mice; Mice, Inbred C57BL; Mice, Knockout; Morphogenesis; Neoplasm Transplantation; Signal Transduction; Skin Transplantation; Transplantation, Heterologous; Kalinin
PubMed: 21067603
DOI: 10.1186/1471-213X-10-112 -
Development (Cambridge, England) Mar 2023The blood-brain barrier (BBB) is a vascular endothelial cell boundary that partitions the circulation from the central nervous system to promote normal brain health. We...
The blood-brain barrier (BBB) is a vascular endothelial cell boundary that partitions the circulation from the central nervous system to promote normal brain health. We have a limited understanding of how the BBB is formed during development and maintained in adulthood. We used quantitative transcriptional profiling to investigate whether specific adhesion molecules are involved in BBB functions, with an emphasis on understanding how astrocytes interact with endothelial cells. Our results reveal a striking enrichment of multiple genes encoding laminin subunits as well as the laminin receptor gene Itga7, which encodes the alpha7 integrin subunit, in astrocytes. Genetic ablation of Itga7 in mice led to aberrant BBB permeability and progressive neurological pathologies. Itga7-/- mice also showed a reduction in laminin protein expression in parenchymal basement membranes. Blood vessels in the Itga7-/- brain showed separation from surrounding astrocytes and had reduced expression of the tight junction proteins claudin 5 and ZO-1. We propose that the alpha7 integrin subunit in astrocytes via adhesion to laminins promotes endothelial cell junction integrity, all of which is required to properly form and maintain a functional BBB.
Topics: Mice; Animals; Blood-Brain Barrier; Astrocytes; Laminin; Endothelial Cells; Integrins; Tight Junctions
PubMed: 36960827
DOI: 10.1242/dev.201356 -
Biochemical and Biophysical Research... Oct 2008Laminins are glycoproteins expressed in the basement membrane of multiple epithelial tissues. Previously described purification procedures for the human laminin variants...
Laminins are glycoproteins expressed in the basement membrane of multiple epithelial tissues. Previously described purification procedures for the human laminin variants laminin-5 (LN-332) and laminin-10 (LN-511) use tissue as starting material and have multiple steps. We demonstrate a two-step laminin immunoaffinity purification method to produce consistent quantities of intact and biologically active LN-332 and LN-511 from human keratinocyte (HaCaT) and human lung carcinoma (A549) cell lines, respectively. The purification of LN-332 and LN-551 was demonstrated by PAGE analysis, silver staining and Western blot analysis. The purification procedure includes instruction on removing a cell adhesion contaminant known as galectin-3 binding protein from purified LN-511. The biological activity of purified laminin was tested in a standard cell adhesion assay and compared to commercially available LN-111. This rapid and reproducible purification method will contribute to understanding the role of LN-332 and LN-511 in cell behavior, signaling, and gene expression.
Topics: Antibody Affinity; Cell Adhesion Molecules; Cell Line; Chromatography, Affinity; Culture Media, Conditioned; Humans; Keratinocytes; Laminin; Kalinin
PubMed: 18713621
DOI: 10.1016/j.bbrc.2008.08.029 -
Dermatologic Clinics Jan 2010The laminins are a secreted family of heterotrimeric molecules essential for basement membrane formation, structure, and function. It is now well established that the... (Review)
Review
The laminins are a secreted family of heterotrimeric molecules essential for basement membrane formation, structure, and function. It is now well established that the alpha3 subunit of laminins-332, -321, and -311 plays an important role in mediating epidermal-dermal integrity and is essential for the skin to withstand mechanical stresses. These laminins also regulate cell migration and mechanosignal transduction. This article provides an overview of the gene, transcripts, and protein structures of laminin alpha3. Also discussed are the proposed functions for the alpha3 subunit-containing laminins.
Topics: Cell Adhesion; Cell Movement; Dermis; Desmosomes; Epidermal Cells; Epidermis; Humans; Laminin
PubMed: 19945619
DOI: 10.1016/j.det.2009.10.009 -
Physiological Reviews Jul 2005Endothelial cells of the blood and lymphatic vasculature are polarized cells with luminal surfaces specialized to interact with inflammatory cells upon the appropriate... (Review)
Review
Endothelial cells of the blood and lymphatic vasculature are polarized cells with luminal surfaces specialized to interact with inflammatory cells upon the appropriate stimulation; they contain specialized transcellular transport systems, and their basal surfaces are attached to an extracellular basement membrane. In adult tissues the basement membrane forms a continuous sleeve around the endothelial tubes, and the interaction of endothelial cells with basement membrane components plays an important role in the maintenance of vessel wall integrity. During development, the basement membrane of endothelium provides distinct spatial and molecular information that influences endothelial cell proliferation, migration, and differentiation/maturation. Microvascular endothelium matures into phenotypically distinct types: continuous, fenestrated, and discontinuous, which also differ in their permeability properties. Development of these morphological and physiological differences is thought to be controlled by both soluble factors in the organ or tissue environment and by cell-cell and cell-matrix interactions. Basement membranes of endothelium, like those of other tissues, are composed of laminins, type IV collagens, heparan sulfate proteoglycans, and nidogens. However, isoforms of all four classes of molecules exist, which combine to form structurally and functionally distinct basement membranes. The endothelial cell basement membranes have been shown to be unique with respect to their laminin isoform composition. Laminins are a family of glycoprotein heterotrimers composed of an alpha, beta, and gamma chain. To date, 5alpha, 4beta, and 3gamma laminin chains have been identified that can combine to form 15 different isoforms. The laminin alpha-chains are considered to be the functionally important portion of the heterotrimers, as they exhibit tissue-specific distribution patterns and contain the major cell interaction sites. Vascular endothelium expresses only two laminin isoforms, and their expression varies depending on the developmental stage, vessel type, and the activation state of the endothelium. Laminin 8 (composed of laminin alpha4, beta1, and gamma1 chains) is expressed by all endothelial cells regardless of their stage of development, and its expression is strongly upregulated by cytokines and growth factors that play a role in inflammatory events. Laminin 10 (composed of laminin alpha5, beta1, and gamma1 chains) is detectable primarily in endothelial cell basement membranes of capillaries and venules commencing 3-4 wk after birth. In contrast to laminin 8, endothelial cell expression of laminin 10 is upregulated only by strong proinflammatory signals and, in addition, angiostatic agents such as progesterone. Other extracellular matrix molecules, such as BM40 (also known as SPARC/osteonectin), thrombospondins 1 and 2, fibronectin, nidogens 1 and 2, and collagen types VIII, XV, and XVIII, are also differentially expressed by endothelium, varying with the endothelium type and/or pathophysiological state. The data argue for a dynamic endothelial cell extracellular matrix that presents different molecular information depending on the type of endothelium and/or physiological situation. This review outlines the unique structural and functional features of vascular basement membranes, with focus on the endothelium and the laminin family of glycoproteins.
Topics: Animals; Blood Vessels; Cell Differentiation; Endothelial Cells; Extracellular Matrix; Humans; Laminin; Receptors, Laminin
PubMed: 15987800
DOI: 10.1152/physrev.00014.2004 -
Cell Adhesion & Migration 2013The mechanisms controlling vascular development, both normal and pathological, are not yet fully understood. Many diseases, including cancer and diabetic retinopathy,... (Review)
Review
The mechanisms controlling vascular development, both normal and pathological, are not yet fully understood. Many diseases, including cancer and diabetic retinopathy, involve abnormal blood vessel formation. Therefore, increasing knowledge of these mechanisms may help develop novel therapeutic targets. The identification of novel proteins or cells involved in this process would be particularly useful. The retina is an ideal model for studying vascular development because it is easy to access, particularly in rodents where this process occurs post-natally. Recent studies have suggested potential roles for laminin chains in vascular development of the retina. This review will provide an overview of these studies, demonstrating the importance of further research into the involvement of laminins in retinal blood vessel formation.
Topics: Aging; Animals; Astrocytes; Basement Membrane; Cell Movement; Gene Expression Regulation, Developmental; Humans; Laminin; Mice; Mutation; Protein Binding; Rats; Retina; Retinal Vessels
PubMed: 23154403
DOI: 10.4161/cam.22480 -
Cell Death & Disease May 2018Laminins are heterotrimeric glycoproteins of the extracellular matrix. Eleven different laminin chains have been identified in vertebrates. They are ubiquitously...
Laminins are heterotrimeric glycoproteins of the extracellular matrix. Eleven different laminin chains have been identified in vertebrates. They are ubiquitously expressed in the human body, with a distinct tissue distribution. Laminin expression in neural retina and their functional role during human retinogenesis is still unknown. This study investigated the laminin expression in human developing and adult retina, showing laminin α1, α5, β1, β2 and γ1 to be predominantly expressed in Bruch's membrane and the inner limiting membrane. Laminin-332 and laminin γ3 expression were mainly observed in the neural retina during retinal histogenesis. These expression patterns were largely conserved in pluripotent stem cell-derived retinal organoids. Blocking of laminin γ3 function in retinal organoids resulted in the disruption of laminar organisation and synapse formation, the loss of photoreceptor organisation and retinal ganglion cells. Our data demonstrate a unique temporal and spatial expression for laminins and reveal a novel role for laminin γ3 during human retinogenesis.
Topics: Adult; Aged; Aged, 80 and over; Animals; Biomarkers; Cell Differentiation; Female; Human Embryonic Stem Cells; Humans; Laminin; Macaca; Male; Mice, Inbred C57BL; Neutralization Tests; Organoids; Photoreceptor Cells, Vertebrate; Retinal Ganglion Cells
PubMed: 29795281
DOI: 10.1038/s41419-018-0648-0 -
Frontiers in Bioscience : a Journal and... Jan 2006Laminins are the major constituents of blood vessel basement membranes (BMs). Each laminin is a trimer consisting of three assembled polypeptide chains, alpha, beta and... (Review)
Review
Laminins are the major constituents of blood vessel basement membranes (BMs). Each laminin is a trimer consisting of three assembled polypeptide chains, alpha, beta and gamma. More than 15 laminin isoforms are known to date and the expression of specific isoforms may change in certain pathological conditions. Here we show that during progression of glial tumors laminin-9 (alpha4beta2gamma1) is switched to laminin-8 (alpha4beta1gamma1), which is dramatically increased in glial brain tumors. Laminin-8 overproduction by glial tumor cells facilitates spread of glioma. Brain tumors with laminin-8 overexpression recur faster after standard treatment and patients have shorter survival time. Laminin-8 may be thus used as a predictor of tumor recurrence, patient survival and as a potential molecular target for glioma therapy.
Topics: Animals; Basement Membrane; Biomarkers, Tumor; Brain Neoplasms; Extracellular Matrix; Glioblastoma; Glioma; Humans; In Vitro Techniques; Laminin; Microscopy, Fluorescence; Models, Biological; Neoplasm Invasiveness; Neoplasm Metastasis; Neovascularization, Pathologic; Oligonucleotides, Antisense; Recurrence; Treatment Outcome
PubMed: 16146715
DOI: 10.2741/1781 -
Current Pharmaceutical Design 2009Basement membranes are sheet-like cell-adherent extracellular matrices that serve as cell substrata and solid-phase agonists, contributing to tissue organization,... (Review)
Review
Basement membranes are sheet-like cell-adherent extracellular matrices that serve as cell substrata and solid-phase agonists, contributing to tissue organization, stability and differentiation. These matrices are assembled as polymers of laminins and type IV collagens that are tethered to nidogens and proteoglycans. They bind to cell surface molecules that include signal-transducing receptors such as the integrins and dystroglycan and form attachments to adjacent connective tissues. The cell receptors, in turn, provide links between the matrix and underlying cytoskeleton. Genetic diseases of basement membrane and associated components, collectively the basement membrane zone, disrupt the extracellular matrix and/or its linkages to affect nerve, muscle, skin, kidney and other tissues. These diseases can arise due to a loss of matrix integrity, adhesion strength and/or receptor-mediated signaling. An understanding of the mechanisms of basement membrane zone assembly and resulting structure can provide insights into the development of normal tissues and the pathogenic mechanisms that underlie diverse disorders.
Topics: Agrin; Animals; Basement Membrane; Collagen; Extracellular Matrix Proteins; Heparan Sulfate Proteoglycans; Humans; Laminin; Membrane Glycoproteins; Myelin Sheath; Neuromuscular Diseases; Stromal Cells
PubMed: 19355968
DOI: 10.2174/138161209787846766