Concomitant neoplasms in the skin and stomach unveil the role of type IV collagen and E-cadherin in mucin core protein 5AC expression in vivo

2015 ◽  
Vol 174 (2) ◽  
pp. 395-397
Author(s):  
H. Hata ◽  
K. Natsuga ◽  
S. Kitamura ◽  
K. Imafuku ◽  
Y. Yamaguchi ◽  
...  
Keyword(s):  
Type Iv Collagen ◽  
Core Protein ◽  
Type Iv ◽  
Mucin Core Protein ◽  
E Cadherin

scholarly journals Analysis of the role of Nidogen/entactin in basement membrane assembly and morphogenesis in Drosophila

2018 ◽  
Author(s):  
Jianli Dai ◽  
Beatriz Estrada ◽  
Sofie Jacobs ◽  
Besaiz J. Sánchez-Sánchez ◽  
Jia Tang ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Type Iv Collagen ◽  
Collagen Iv ◽  
Basement Membranes ◽  
Extracellular Matrices ◽  
Tissue Specific ◽  
Type Iv

AbstractBasement membranes (BMs) are thin sheet-like specialized extracellular matrices found at the basal surface of epithelia and endothelial tissues. They have been conserved across evolution and are required for proper tissue growth, organization, differentiation and maintenance. The major constituents of BMs are two independent networks of Laminin and Type IV Collagen interlinked by the proteoglycan Perlecan and the glycoprotein Nidogen/entactin (Ndg). The ability of Ndg to bind in vitro Collagen IV and Laminin, both with key functions during embryogenesis, anticipated an essential role for Ndg on morphogenesis linking the Laminin and Collagen IV networks. This was supported by results from in vitro and cultured embryonic tissues experiments. However, the fact that elimination of Ndg in C. elegans and mice did not affect survival, strongly questioned this proposed linking role. Here, we have isolated mutations in the only Ndg gene present in Drosophila. We find that while, similar to C.elegans and mice, Ndg is not essential for overall organogenesis or viability, it is required for appropriate fertility. We also find, alike in mice, tissue-specific requirements of Ndg for proper assembly and maintenance of certain BMs, namely those of the adipose tissue and flight muscles. In addition, we have performed a thorough functional analysis of the different Ndg domains in vivo. Our results support an essential requirement of the G3 domain for Ndg function and unravel a new key role for the Rod domain in regulating Ndg incorporation into BMs. Furthermore, uncoupling of the Laminin and Collagen IV networks is clearly observed in the larval adipose tissue in the absence of Ndg, indeed supporting a linking role. In light of our findings, we propose that BM assembly and/or maintenance is tissue-specific, which could explain the diverse requirements of a ubiquitous conserved BM component like Nidogen.Author SummaryBasement membranes (BMs) are thin layers of specialized extracellular matrices present in every tissue of the human body. Its main constituents are two networks of Laminin and Type IV Collagen linked by Nidogen (Ndg) and proteoglycans. They form an organized scaffold that regulates organ morphogenesis and function. Mutations affecting BM components are associated with organ dysfunction and several congenital diseases. Thus, a better comprehension of BM assembly and maintenance will not only help to learn more about organogenesis but also to a better understanding and, hopefully, treatment of these diseases. Here, we have used Drosophila to analyse the role of Ndg in BM formation in vivo. Elimination of Ndg in worms and mice does not affect survival, strongly questioning its proposed linking role, derived from in vitro experiments. Here, we show that in the fly Ndg is dispensable for BM assembly and preservation in many tissues, but absolutely required in others. Furthermore, our functional study of the different Ndg domains challenges the significance of some interactions between BM components derived from in vitro experiments, while confirming others, and reveals a new key requirement for the Rod domain in Ndg function and incorporation into BMs.

scholarly journals Shift in collagen type as an early response to induction of the metanephric mesenchyme.

1981 ◽  
Vol 89 (2) ◽  
pp. 276-283 ◽  
Author(s):  
P Ekblom ◽  
E Lehtonen ◽  
L Saxén ◽  
R Timpl
Keyword(s):  
Basal Lamina ◽  
Type Iv Collagen ◽  
Early Response ◽  
Type I ◽  
Metanephric Mesenchyme ◽  
Type Iv ◽  
Interstitial Collagens ◽  
Membrane Components

Conversion of the nephrogenic mesenchyme into epithelial tubules requires an inductive stimulus from the ureter bud. Here we show with immunofluorescence techniques that the undifferentiated mesenchyme before induction expresses uniformly type I and type III collagens. Induction both in vivo and in vitro leads to a loss of these proteins and to the appearance of basement membrane components including type IV collagen. This change correlates both spatially and temporally with the determination of the mesenchyme and precedes and morphological events. During morphogenesis, type IV collagen concentrates at the borders of the developing tubular structures where, by electron microscopy, a thin, often discontinuous basal lamina was seen to cover the first pretubular cell aggregates. Subsequently, the differentiating tubules were surrounded by a well-developed basal lamina. No loss of the interstitial collagens was seen in the metanephric mesenchyme when brought into contact with noninducing tissues or when cultured alone. Similar observations were made with nonnephrogenic mesenchyme (salivary, lung) when exposed to various heterotypic tissues known to induce tubules in the nephrogenic mesenchyme. The sequential shift in the composition of the extracellular matrix from an interstitial, mesenchymal type to a differentiated, epithelial type is so far the first detectable response of the nephrogenic mesenchyme to the tubule-inducing signal.

scholarly journals Perlecan regulates Oct-1 gene expression in vascular smooth muscle cells.

1997 ◽  
Vol 8 (6) ◽  
pp. 999-1011 ◽  
Author(s):  
M C Weiser ◽  
N A Grieshaber ◽  
P E Schwartz ◽  
R A Majack
Keyword(s):  
Gene Expression ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Type Iv Collagen ◽  
Muscle Cells ◽  
Mrna Levels ◽  
Type Iv

Vascular smooth muscle cells (SMCs) are very quiescent in the mature vessel and exhibit a remarkable phenotype-dependent diversity in gene expression that may reflect the growth responsiveness of these cells under a variety of normal and pathological conditions. In this report, we describe the expression pattern of Oct-1, a member of a family of transcription factors involved in cell growth processes, in cultured and in in vivo SMCs. Oct-1 mRNA was undetectable in the contractile-state in vivo SMCs; was induced upon disruption of in vivo SMC-extracellular matrix interactions; and was constitutively expressed by cultured SMCs. Oct-1 transcripts were repressed when cultured SMCs were plated on Engelbreth-Holm-Swarm tumor-derived basement membranes (EHS-BM) but were rapidly induced after disruption of SMC-EHS-BM contacts; reexpression was regulated at the transcriptional level. To identify the EHS-BM component involved in the active repression of Oct-1 mRNA expression, SMCs were plated on laminin, type IV collagen, fibronectin, or perlecan matrices. Oct-1 mRNA levels were readily detectable when SMCs were cultured on matrices composed of laminin, type IV collagen, or fibronectin but were repressed when SMCs were cultured on perlecan matrices. Finally, the Oct-1-suppressing activity of EHS-BM was sensitive to heparinase digestion but not to chondroitinase ABC or hyaluronidase digestion, suggesting that the heparan sulfate side chains of perlecan play a biologically important role in negatively regulating the expression of Oct-1 transcripts.

scholarly journals DHHC7-mediated palmitoylation of the accessory protein barttin critically regulates the functions of ClC-K chloride channels

2020 ◽  
Vol 295 (18) ◽  
pp. 5970-5983 ◽  
Author(s):  
Nataliya Gorinski ◽  
Daniel Wojciechowski ◽  
Daria Guseva ◽  
Dalia Abdel Galil ◽  
Franziska E. Mueller ◽  
...  
Keyword(s):  
Chloride Channels ◽  
Bartter Syndrome ◽  
Post Translational Modification ◽  
Salt Diet ◽  
Type Iv ◽  
Low Salt ◽  
Accessory Subunit ◽  
Palmitoyl Acyltransferase

Barttin is the accessory subunit of the human ClC-K chloride channels, which are expressed in both the kidney and inner ear. Barttin promotes trafficking of the complex it forms with ClC-K to the plasma membrane and is involved in activating this channel. Barttin undergoes post-translational palmitoylation that is essential for its functions, but the enzyme(s) catalyzing this post-translational modification is unknown. Here, we identified zinc finger DHHC-type containing 7 (DHHC7) protein as an important barttin palmitoyl acyltransferase, whose depletion affected barttin palmitoylation and ClC-K-barttin channel activation. We investigated the functional role of barttin palmitoylation in vivo in Zdhhc7−/− mice. Although palmitoylation of barttin in kidneys of Zdhhc7−/− animals was significantly decreased, it did not pathologically alter kidney structure and functions under physiological conditions. However, when Zdhhc7−/− mice were fed a low-salt diet, they developed hyponatremia and mild metabolic alkalosis, symptoms characteristic of human Bartter syndrome (BS) type IV. Of note, we also observed decreased palmitoylation of the disease-causing R8L barttin variant associated with human BS type IV. Our results indicate that dysregulated DHHC7-mediated barttin palmitoylation appears to play an important role in chloride channel dysfunction in certain BS variants, suggesting that targeting DHHC7 activity may offer a potential therapeutic strategy for reducing hypertension.

scholarly journals Retraction Note: Type IV collagen α1-chain noncollagenous domain blocks MMP-2 activation both in-vitro and in-vivo

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Yakkanti Akul Sudhakar ◽  
Raj Kumar Verma ◽  
Smita C. Pawar
Keyword(s):  
Type Iv Collagen ◽  
Link Type ◽  
Type Iv

Editor's Note: this Article has been retracted; the Retraction Note is available at https://www.nature.com/articles/s41598-020-76500-9

Peritoneal Injury by Methylglyoxal in Peritoneal Dialysis

2006 ◽  
Vol 26 (3) ◽  
pp. 380-392 ◽  
Author(s):  
Ichiro Hirahara ◽  
Eiji Kusano ◽  
Satoru Yanagiba ◽  
Yukio Miyata ◽  
Yasuhiro Ando ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Basement Membrane ◽  
Structural Changes ◽  
Type Iv Collagen ◽  
Degradation Products ◽  
Abdominal Cocoon ◽  
Type Iv ◽  
Type Iv Collagen 7S ◽  
Peritoneal Function

Background Peritoneal dialysis (PD) is a common treatment for patients with reduced or absent renal function. Long-term PD leads to peritoneal injury with structural changes and functional decline, such as ultrafiltration loss. At worst, peritoneal injury leads to encapsulating peritoneal sclerosis, a serious complication of PD. Glucose degradation products contained in PD fluids contribute to the bioincompatibility of conventional PD fluids. Methylglyoxal (MGO) is an extremely toxic glucose degradation product. The present study examined the injurious effect of MGO on peritoneum in vivo. Methods Male Sprague–Dawley rats ( n = 6) were administered PD fluids (pH 5.0) containing 0, 0.66, 2, 6.6, or 20 mmol/L MGO every day for 21 days. On day 22, peritoneal function was estimated by the peritoneal equilibration test. Drained dialysate was analyzed for type IV collagen-7S, matrix metalloproteinase (MMP), and vascular endothelial growth factor (VEGF). Histological analysis was also performed. Results In rats receiving PD fluids containing more than 0.66 mmol/L MGO, peritoneal function decreased significantly and levels of type IV collagen-7S and MMP-2 in drained dialysate increased significantly. In the 20-mmol/L MGO-treated rats, loss of body weight, expression of VEGF, thickening of the peritoneum, and formation of abdominal cocoon were induced. MMP-2 and VEGF were produced by infiltrating cells in the peritoneum. Type IV collagen was detected in basement membrane of microvessels. Conclusion MGO induced not only peritoneal injury but also abdominal cocoon formation in vivo. The decline of peritoneal function may result from reconstitution of microvessel basement membrane or neovascularization.

scholarly journals Agrin-induced reorganization of extracellular matrix components on cultured myotubes: relationship to AChR aggregation.

1990 ◽  
Vol 111 (3) ◽  
pp. 1161-1170 ◽  
Author(s):  
R M Nitkin ◽  
T C Rothschild
Keyword(s):  
Extracellular Matrix ◽  
Type Iv Collagen ◽  
Neuromuscular Junctions ◽  
Synaptic Organization ◽  
Type Iv ◽  
Extracellular Matrix Components ◽  
Cultured Myotubes ◽  
Matrix Components ◽  
Induced Aggregation

Agrin, an extracellular matrix-associated protein extracted from synapse-rich tissues, induces the accumulation of acetylcholine receptors (AChRs) and other synaptic components into discrete patches on cultured myotubes. The appearance of agrin-like molecules at neuromuscular junctions suggests that it may direct synaptic organization in vivo. In the present study we examined the role of extracellular matrix components in agrin-induced differentiation. We used immunohistochemical techniques to visualize the spatial and temporal distribution of laminin, a heparan sulfate proteoglycan (HSPG), fibronectin, and type IV collagen on cultured chick myotubes during agrin-induced aggregation of AChRs. Myotubes displayed significant amounts of laminin and HSPG, lesser amounts of type IV collagen, and little, if any, fibronectin. Agrin treatment caused cell surface laminin and HSPG to patch, while collagen and fibronectin distributions were generally unaffected. Many of the agrin-induced laminin and HSPG patches colocalized with AChR patches, raising the possibility of a causal relationship between matrix patching and AChR accumulations. However, patching of AChRs (complete within a few hours) preceded that of laminin or HSPG (not complete until 15-20 h), making it unlikely that matrix accumulations initiate AChR patching at agrin-induced sites. Conversely, when AChR patching was blocked by treatment with anti-AChR antibody mAb 35, agrin was still able to effect patching of laminin and HSPG. Taken together, these findings suggest that agrin-induced accumulations of AChR and laminin/HSPG are not mechanistically linked.

VWF Interaction With Type IV Collagen Is Mediated Through Critical VWF A1 Domain Residues

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 29-29
Author(s):  
Veronica H. Flood ◽  
Abraham C. Schlauderaff ◽  
Paula M. Jacobi ◽  
Tricia L. Slobodianuk ◽  
Robert R. Montgomery ◽  
...  
Keyword(s):  
Binding Sites ◽  
Type Iv Collagen ◽  
Platelet Glycoprotein ◽  
Collagen Binding ◽  
Common Component ◽  
Type Iv ◽  
Static Conditions ◽  
A1 Domain ◽  
Von Willebrand

Abstract Von Willebrand factor (VWF) plays a key role in coagulation by tethering platelets to injured subendothelium via binding sites for platelet glycoprotein Ib and collagen. The binding sites for types I and III collagen in the VWF A3 domain are well characterized, and defects in this region have been implicated in von Willebrand disease (VWD). Additional collagens present in the vasculature may also be involved in interactions with VWF. A VWF A1 sequence variation, p.R1399H, has been associated with decreased binding to type VI collagen, but the clinical significance of this observation remains unclear. Type IV collagen is a common component of the basement membrane and as such may be an important ligand for VWF. While some VWD testing utilizes types I or III collagen, current clinical testing does not include collagen IV or VI. To characterize the role of the VWF A1 domain in VWF-type IV collagen interactions, we generated several A1 domain variant human and/or murine recombinant VWF (rVWF) constructs including R1399H and several type 2M VWD variants localized to the same region (S1387I, Q1402P, and an 11 amino acid deletion mutant encompassing amino acids 1392-1402). These constructs were then expressed in HEK 293T cells. To further assess the role of the A1 domain, scanning alanine mutagenesis (SAM) of residues 1387 through 1412 was conducted. VWF antigen levels (VWF:Ag), collagen binding with type III (VWF:CB3), IV (VWF:CB4), or VI (VWF:CB6) collagen were determined, and multimer distribution was assessed for all recombinant VWF variants. The role of R1399H in the context of human rVWF was characterized initially. Although VWF:Ag, VWF:CB3, and multimer distribution were normal for R1399H compared to wild-type (WT VWF), VWF:CB4 was undetectable. To examine this effect in a mouse model, the R1399H variant was expressed in the context of murine rVWF and collagen binding was determined. Similar to the human variant, murine R1399H rVWF demonstrated significantly reduced binding to murine type IV collagen, at only 7% of the binding seen with WT murine rVWF. In order to examine the behavior of R1399H under shear conditions, either WT or R1399H murine rVWF DNA was hydrodynamically injected into the tail veins of VWF -/- mice to induce expression of the proteins; blood was drawn from the vena cava 24 hours later and then examined on the VenaFlux flow apparatus. VWF expression levels and multimer distribution were similar for the R1399H- and WT-injected mice. Under static conditions, the murine plasma-derived R1399H demonstrated decreased VWF:CB4, at only 16% of the levels seen with WT VWF. No defect was seen in VWF:CB3. Furthermore, when binding to type IV collagen was assessed under flow conditions by VenaFlux, platelet adhesion was significantly decreased in mice expressing R1399H VWF as compared to mice expressing WT VWF. When examining other A1 domain variants, Q1402P and del1392-1402 demonstrated absent VWF:CB4 while S1387I demonstrated a significant reduction in VWF:CB4 compared to WT VWF. All SAM VWF A1 domain variants demonstrated normal expression, multimerization, and VWF:CB3. However, type IV collagen binding was absent for R1392A, R1395A, R1399A, and K1406A and was reduced to less than 50% of WT VWF for Q1402A, K1405A, and K1407A. These residues map to an outside face of the VWF A1 domain crystal structure, and are likely the critical residues for VWF binding to type IV collagen. Taken together, these data demonstrate that the type IV collagen binding site localizes to a specific region of the VWF A1 domain. Mutations in this region of VWF may be clinically significant due to a defect in the ability of VWF to attract platelets to exposed type IV collagen which may contribute to bleeding symptoms seen in VWD. Disclosures: No relevant conflicts of interest to declare.

Sign in / Sign up

Export Citation Format

Share Document