scholarly journals Isoform switching of type IV collagen is developmentally arrested in X-linked Alport syndrome leading to increased susceptibility of renal basement membranes to endoproteolysis.

1997 ◽  
Vol 99 (10) ◽  
pp. 2470-2478 ◽  
Author(s):  
R Kalluri ◽  
C F Shield ◽  
P Todd ◽  
B G Hudson ◽  
E G Neilson
Keyword(s):  
Alport Syndrome ◽  
Type Iv Collagen ◽  
Basement Membranes ◽  
Type Iv ◽  
Isoform Switching ◽  
Increased Susceptibility

Contribution of the Minor Chain Type IV Collagen Network to the Mechanics of the Ocular Lens Capsule

2012 ◽  
Author(s):  
Lazarina Gyoneva ◽  
Yoav Segal ◽  
Kevin D. Dorfman ◽  
Victor H. Barocas
Keyword(s):  
Alport Syndrome ◽  
Type Iv Collagen ◽  
Dry Weight ◽  
Hereditary Disease ◽  
Collagen Iv ◽  
Lens Capsule ◽  
Basement Membranes ◽  
Ocular Lens ◽  
Ocular Manifestations ◽  
Type Iv

The ocular lens capsule (LC) is a specialized basement membrane which completely surrounds the lens. The LC serves as an attachment point for lens epithelial and fiber cells, controls lens solute and water transport, and makes accommodation possible [1]. It is primarily composed of type IV collagen (65% of dry weight), laminin, nidogen, and proteoglycans, of which type IV collagen is the main-tension resisting element [1,2]. Collagen IV monomers organize into polygonal planar networks resembling chicken wire (Fig.1) [3]. There are six different collagen IV monomers, labeled α1(IV) to α6(IV) each produced by a separate gene – COL4A1 to COL4A6. Monomers form triple helical protomers in a highly selective manner. In nature, only three monomer combinations have been discovered: the [α1(IV)]2α2(IV) protomer, referred to as the major chain, is found in all basement membranes; the α3(IV)α4(IV)α5(IV) protomer (minor chain) is found only in few basement membranes including the LC; the [α5(IV)]2α6(IV) protomer is very rare and will not be discussed further. Protomers of the same type assemble with one another to form separate networks which are known to have some differences [4]. For example, the minor chain network is more cross-linked than the major chain network. In a hereditary disease called Alport syndrome, the minor chain network is completely missing in males due to a mutation in the COL4A5 gene (located on the X chromosome) which prevents production of the α5(IV) monomer. Male Alport syndrome patients have significant ocular manifestations such as anterior lenticonus (protrusion of the lens), cataract, and even lens rupture [5] and they exhibit significant thinning of the LC. Because 1) the minor network is more cross-linked than the major network, 2) its absence affects lens shape, and 3) the LC displays pathological disruptions when it is missing, we theorize that its presence confers additional mechanical strength to the LC. Therefore, the objective of this study is to assess the contribution of the minor chain network to the mechanics of the LC.

scholarly journals Distribution of α‐chains of type IV collagen in glomerular basement membranes with ultrastructural alterations suggestive of Alport syndrome

2001 ◽  
Vol 16 (5) ◽  
pp. 945-952 ◽  
Author(s):  
Paola Barsotti ◽  
Andrea Onetti Muda ◽  
Gianna Mazzucco ◽  
Laura Massella ◽  
Bruno Basolo ◽  
...  
Keyword(s):  
Alport Syndrome ◽  
Type Iv Collagen ◽  
Basement Membranes ◽  
Ultrastructural Alterations ◽  
Type Iv

scholarly journals Abnormal Glomerular Basement Membrane Laminins in Murine, Canine, and Human Alport Syndrome: Aberrant Laminin α2 Deposition Is Species Independent

2001 ◽  
Vol 12 (2) ◽  
pp. 252-260
Author(s):  
CLIFFORD E. KASHTAN ◽  
YOUNGKI KIM ◽  
GEORGE E. LEES ◽  
PAUL S. THORNER ◽  
ISMO VIRTANEN ◽  
...  
Keyword(s):  
Alport Syndrome ◽  
Type Iv Collagen ◽  
Critical Role ◽  
Basement Membranes ◽  
Type Iv ◽  
Normal Human ◽  
Composition Structure ◽  
Type V ◽  
And Function ◽  
Laminin Α2

Abstract. Kidneys from mice, dogs, and humans with X-linked and autosomal-recessive forms of Alport syndrome were examined by immunofluorescence for expression of laminin α, β, and γ chains using monospecific antibodies. Laminin α2 chain was absent from glomerular basement membranes (GBM) in normal human, murine, and canine kidneys but was abnormally deposited in Alport GBM, regardless of species or inheritance pattern. In murine and canine Alport kidneys, laminin α2 seems to be deposited as part of both laminin-2 (α2β1γ1) and laminin-4 (α2β2γ1) but as part of only laminin-4 in human Alport kidneys. GBM laminin α2 chain deposition was not observed in a variety of non-Alport human glomerulopathies. This finding adds to the list of proteins that are aberrantly deposited in Alport GBM as a consequence of the absence of the α3, α4, and α5 chains of type IV collagen: (1) type IV collagen α1 and α2 chains, (2) type V collagen, (3) type VI collagen, and most recently (4) the laminin α2 chain and (5) the laminin α1 and β1 chains in mice and dogs. These findings emphasize further the critical role played by the α3, α4, and α5 chains of type IV collagen in establishing and maintaining the composition, structure, and function of mature GBM.

scholarly journals The Genetics, Current Research, and Future Treatment of Alport Syndrome

2017 ◽  
Vol 6 (1) ◽  
pp. 1-7
Author(s):  
Elise Alexandra Kikis ◽  
Emily Holland Williams
Keyword(s):  
Basement Membrane ◽  
End Stage Renal Disease ◽  
Alport Syndrome ◽  
Autosomal Recessive ◽  
Type Iv Collagen ◽  
Autosomal Dominant ◽  
Basement Membranes ◽  
Type Iv ◽  
Stage Renal Disease ◽  
End Stage

Alport syndrome is a type IV collagen disease that affects the glomerular basement membrane of approximately one in every 5000 people. The disease was first described by A. Cecil Alport in 1927 as “a dominantly inherited hereditary nephritis.” The three genotypes of the disease are X-linked dominant, autosomal recessive, and autosomal dominant. The X-linked dominant genotype is the most common, accounting for 80% of all cases of Alport syndrome, affecting mainly men. The autosomal recessive and autosomal dominant types affect men and women equally. Alport syndrome is caused by mutations on the COL4A3, COL4A4, and COL4A5 genes, which code the ?3, ?4, and ?5 (IV) chains that make up type IV collagen molecules, an important component of basement membranes. Thus, Alport syndrome results in malformed basement membranes, with symptoms including renal impairment, hematuria, bilateral sensorineural hearing loss, and an abnormal structure of the glomerular basement membrane. Alport syndrome also often progresses to end-stage renal disease, especially in men with X-linked Alport syndrome. At this point, there is no cure for Alport syndrome. However, there are many successful treatments for its symptoms. Angiotensin-converting enzyme (ACE) inhibitors are often given to patients in the early stages of Alport syndrome. For patients with end-stage renal disease, dialysis or kidney transplants are considered the best course of action.

Type IV Collagen Immunostaining Is a Simple, Reliable Diagnostic Tool for Distinguishing Between Adenomatous and Normal Pituitary Glands

2007 ◽  
Vol 131 (6) ◽  
pp. 931-935 ◽  
Author(s):  
Jason Jarzembowski ◽  
Ricardo Lloyd ◽  
Paul McKeever
Keyword(s):  
Pituitary Adenomas ◽  
Type Iv Collagen ◽  
Basement Membranes ◽  
Immunohistochemical Detection ◽  
Secondary Effects ◽  
Hormone Production ◽  
Clonal Population ◽  
Normal Gland ◽  
Type Iv ◽  
Pituitary Glands

Abstract Context.—Pituitary adenomas are clinically diagnosed based on radiologic studies and/or secondary effects of hormone production. Definitive pathologic identification relies on immunohistochemical detection of a clonal population of hormone-producing cells. However, not all adenomas secrete hormones, so performing a battery of stains is inefficient. Reports have shown decreased type IV collagen in the stroma of other epithelial tumors. Objective.—To validate type IV collagen immunohistochemistry as a diagnostic method. Design.—We immunostained 27 adenomas and 19 normal pituitaries. The areas with the sparsest type IV collagen fibers were viewed at 3 magnifications (×10, ×20, and ×40 objectives), counting 1, 3, or 10 microscopic fields. A field was scored as “traversable” if a path existed from any point on the periphery of the field to a point on the approximately opposite periphery that did not cross any stained fibers. Results were compared with reticulin staining and to the existing diagnosis previously determined by histology, hormone immunostaining, and clinical correlation. Results.—Adenomas have less type IV collagen in their basement membranes, leading to sparser, trabecular staining in neoplasms versus a more rigid meshwork pattern in normal glands. One might envision the stained fibers as maze walls—one can traverse medium-powered fields in an adenoma, but one hits dead ends and gets trapped in those of a normal gland. Finding a single representative ×10 field to be traversable was 97.5% sensitive and 96.5% specific for an adenoma. Reticulin staining yielded identical results. Conclusions.—Type IV collagen immunostaining is a simple and reliable method of diagnosing pituitary adenomas.

The relationship between emerging neural crest cells and basement membranes in the trunk of the mouse embryo: a TEM and immunocytochemical study

Development ◽  
1986 ◽  
Vol 98 (1) ◽  
pp. 251-268
Author(s):  
J. Sternberg ◽  
S. J. Kimber
Keyword(s):  
Neural Crest ◽  
Neural Tube ◽  
Cell Shape ◽  
Type Iv Collagen ◽  
Neural Crest Cell ◽  
Basement Membranes ◽  
Type Iv ◽  
Transmission Electron ◽  
The Relationship ◽  
Crest Cell

The earliest stage of neural crest cell (NCC) migration is characterized by an epitheliomesenchymal transformation, as the cells leave the neural tube. There is evidence that in a number of cell systems this transformation is accompanied by alteration or depletion of associated basement membranes. This study examines the ultrastructural relationship between mouse NCCs and adjacent basement membranes during the earliest stages of migration from the neural tube. Basement membranes were identified by transmission electron microscopy (TEM) and immunofluorescence using antibodies to type-IV collagen. The ultrastructural features of NCCs and their relationship with surrounding tissues were also examined using TEM. In the dorsal region of the neural tube, from which NCCs originate, the basement membrane was depleted or absent, and with the immunofluorescence technique it was shown that this pattern was reflected in a deficit of type-IV collagen. TEM observations indicated that ultrastructurally NCCs differ from their neuroepithelial neighbours only in overall cell shape and their relationship to other cells and the extracellular matrix.

scholarly journals Inhibition of laminin self-assembly and interaction with type IV collagen by antibodies to the terminal domain of the long arm.

1986 ◽  
Vol 103 (5) ◽  
pp. 1689-1697 ◽  
Author(s):  
A S Charonis ◽  
E C Tsilibary ◽  
T Saku ◽  
H Furthmayr
Keyword(s):  
Self Assembly ◽  
Binding Sites ◽  
Type Iv Collagen ◽  
Specific Interaction ◽  
Basement Membranes ◽  
Complex Domain ◽  
Peptide Fragment ◽  
Type Iv ◽  
Collagen Molecules

Laminin is a major glycoprotein of the basement membrane. Although its precise localization and orientation within this structure is unknown, it is presumably anchored to other macromolecules such as type IV collagen or proteoheparan sulfate. In vitro, laminin has the ability to self-assemble and to bind to type IV collagen molecules at distinct sites. To identify more precisely the domains of the complex, cross-shaped laminin molecule that are involved in these interactions, images of laminin-laminin dimers and laminin-type IV collagen complexes obtained by the rotary shadowing method were analyzed. We observed that the complex domain at the end of the long arm of laminin is predominantly involved in these interactions. By using Fab fragments of antibodies specific for a peptide fragment derived from this complex domain, it is shown that laminin self-assembly is inhibited in their presence, as measured by turbidity and by electron microscopy. In addition, these antibodies inhibit the specific interaction of laminin with type IV collagen. These data suggest that the complex domain at the end of the long arm of laminin contains binding sites of potential importance for the assembly of basement membranes.

scholarly journals Expression of collagen type IV in human kidney during prenatal development

2020 ◽  
pp. 111-111
Author(s):  
Vladimir Petrovic ◽  
Ivan Nikolic ◽  
Marko Jovic ◽  
Vladimir Zivkovic ◽  
Miodrag Jocic ◽  
...  
Keyword(s):  
Type Iv Collagen ◽  
Collagen Type ◽  
Kidney Tissue ◽  
Volume Density ◽  
Collagen Iv ◽  
Basement Membranes ◽  
Collagen Type Iv ◽  
Type Iv ◽  
Metanephric Kidney ◽  
Collecting System

Background / Aim. Type IV collagen belongs to the group of non-fibrillar collagens and is an important component of the basement membranes where it accounts for approximately 50% of its structural elements. The aim of the paper was to describe the expression and distribution of collagen type IV in embryonic and fetal metanephric kidney, and to determine the volume density of collagen type IV in kidney tissue in each trimester of development. Methods. The material consisted of 19 human embryos/fetuses, in the gestational age from 8th to 37th week. Kidney tissue specimens were routinely processed to paraffin molds and stained with hematoxylin and eosin and immunohistochemically using polyclonal anti-collagen IV antibody. Stained slides were examined using light microscope and images of the selected areas, under different lens magnification were captured with digital camera. Volume density of collagen type IV was determined by using ImageJ 1.48v and a plugin of the software which inserted a grid system with 336 points. For the data comparison One-Way Analysis of Variance was used. Results. Strong collagen IV immunopositivity was seen in all specimens, with a distribution in the basement membranes of urinary bud, parietal leaf of Bowman?s capsule, glomerular basement membrane, basement membrane of interstitial blood vessels, and basement membranes of nephron tubules and collecting ducts. No statistically significant difference in the volume density of type IV collagen was found between the different trimesters of development. Conclusion. The synthesis and secretion of collagen type IV simultaneously follows the development of nephron structures, collecting system and blood vessels. The volume density of collagen type IV remains constant throughout all the trimesters of metanephric kidney development, indicating that it plays a crucial role in normal development of nephron and collecting system structures, as well as in maintaining the normal kidney function.

The Basement Membranes in Sarcomatoid Carcinomas. An Immunohistochemical Study

1993 ◽  
Vol 79 (2) ◽  
pp. 128-132 ◽  
Author(s):  
Marcello Guarino ◽  
Salvatore Squillaci ◽  
Domenico Reale ◽  
Giorgio Micoli
Keyword(s):  
Immunohistochemical Staining ◽  
Type Iv Collagen ◽  
Immunohistochemical Study ◽  
Staining Pattern ◽  
Complete Loss ◽  
Basement Membranes ◽  
Sarcomatous Component ◽  
Tissue Sections ◽  
Type Iv ◽  
Frequent Finding

Aims Eight sarcomatoid carcinomas from various anatomical locations were investigated by immunohistochemical staining to laminin, type IV collagen and heparan sulfate proteoglycan, to study the characteristics of basement membranes at the interface between carcinomatous and sarcomatous tissues. Methods Paraffin wax embedded tissue sections from representative tumor samples have been stained with specific antibodies, using the peroxidase-antiperoxidase technique. Results In all cases several interruptions or discontinuities of the basement membrane staining pattern were seen. In 4 cases, larger defects or complete loss of staining was also noted. At these places, the boundaries between carcinomatous and sarcomatous tissue were often blurred. Conclusions Disruption and loss of basement membranes at interface between carcinomatous and sarcomatous tissues is a frequent finding in sarcomatoid carcinomas. These changes could be consistent with an epithelial origin of the sarcomatous component in these tumors by means of an epithelial-mesenchymal conversion mechanism.

scholarly journals The pathogenesis of Alport syndrome involves type IV collagen molecules containing the α3(IV) chain: Evidence from anti-GBM nephritis after renal transplantation

1992 ◽  
Vol 42 (1) ◽  
pp. 179-187 ◽  
Author(s):  
Billy G. Hudson ◽  
Raghuram Kalluri ◽  
Sripad Gunwar ◽  
Manfred Weber ◽  
Fernando Ballester ◽  
...  
Keyword(s):  
Renal Transplantation ◽  
Alport Syndrome ◽  
Type Iv Collagen ◽  
Type Iv ◽  
Collagen Molecules
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