HANAC Col4a1 Mutation in Mice Leads to Skeletal Muscle Alterations due to a Primary Vascular Defect

Guiraud, Simon; Migeon, Tiffany; Ferry, Arnaud; Chen, Zhiyong; Ouchelouche, Souhila; Verpont, Marie-Christine; Sado, Yoshikazu; Allamand, Valérie; Ronco, Pierre; Plaisier, Emmanuelle

doi:10.1016/j.ajpath.2016.10.020

Cited by 32 publications

(34 citation statements)

References 33 publications

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“…COL4A1 mutations have been reported to be implicated in several vessel diseases, including familial kidney disease, brain stroke, myocardial infarction, and chronic kidney disease . Moreover, COL4A1 mutations resulted in an excess of the apoptosis of endothelial cells contributing to primary endothelial cell defects and COL4A1 ‐related myopathy in mice . In 2016 it was shown that upregulated COL4A1 had all homozygotes of minor alleles at single nucleotide variants in lymphoblastoid cell lines .…”

Section: Discussionmentioning

confidence: 99%

“…29 Moreover, COL4A1 mutations resulted in an excess of the apoptosis of endothelial cells contributing to primary endothelial cell defects and COL4A1-related myopathy in mice. 30 In 2016 it was shown that upregulated COL4A1 had all homozygotes of minor alleles at single nucleotide variants in lymphoblastoid cell lines. 31 Because COL4A1 synthesizes a major complex of plasma membrane and activates fibroblasts through the PI3K/AKT pathway, it might be a candidate gene for predicting patients' genetic susceptibility to cancer and could be used in targeted cancer therapy.…”

Section: Discussionmentioning

confidence: 99%

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Bioinformatics analysis suggests that COL4A1 may play an important role in gastric carcinoma recurrence

Wang

Chang

et al. 2019

J of Digest Diseases

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Objective Cancer recurrence is a complicated problem for clinicians that contributes to poor prognosis. This study aimed to use advanced gastric carcinoma genes profiles to predict increased risk of cancer recurrence in order to identify patients in need of adjuvant therapy for prognosis improvement. Methods Differentially expressed genes were identified for advanced gastric carcinoma by analyzing the GSE2685 from the Gene Expression Omnibus database (GEO) using R package. The candidate genes were then obtained by gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, protein‐protein interaction analysis and survival analysis. Logistic regression analysis was performed to determine the relationship between candidate genes and the recurrence of gastric carcinoma. Results Collagen type IV alpha 1 (COL4A1) was overexpressed in gastric carcinoma tissue by analyzing the GSE2685 gene expression profiles from the Gene Expression Omnibus database. COL4A1 was also overexpressed in gastric carcinoma tissue from the Cancer Genome Atlas dataset and further determined that higher COL4A1 expression led to poorer overall survival. A univariate analysis suggested that COL4A1 was strongly correlated with T stage and gastric carcinoma recurrence (P = 0.014 and 0.041, respectively). Moreover, a multiple logistic regression analysis indicated that COL4A1 was significantly associated with gastric carcinoma recurrence (hazard ratio 1.605, 95% confidence interval 1.063‐2.677, P = 0.008). Conclusions COL4A1 may promote gastric carcinoma recurrence and could be used as a therapeutic target for gastric carcinoma recurrence.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Bioinformatics analysis suggests that COL4A1 may play an important role in gastric carcinoma recurrence

Wang

Chang

et al. 2019

J of Digest Diseases

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“…The COL4A1 G498V mutation has been previously identified in a human family with cerebral bleeds, renal cysts, muscle cramps, and retinal arterial tortuosity . Recent studies indicate that G498V mutant mice are viable and similarly develop renal cysts, muscular dystrophy, and retinal arterial tortuosity , suggesting that this knock‐in mouse model represents a valuable and relevant model for studying the pathogenesis of COL4A1 disease.…”

Section: Introductionmentioning

confidence: 96%

Severity of arterial defects in the retina correlates with the burden of intracerebral haemorrhage in COL4A1‐related stroke

Ratelade

Mezouar

Domenga-Denier

et al. 2018

The Journal of Pathology

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Mutations in the α1 (COL4A1) or α2 (COL4A2) chains of collagen type IV, a major component of the vascular basement membrane, cause intracerebral haemorrhages with variable expressivity and reduced penetrance by mechanisms that remain poorly understood. Here we sought to investigate the cellular mechanisms of COL4A1-related intracerebral haemorrhage and identify a marker for haemorrhage risk stratification. A combination of histological, immunohistochemical, and electron microscopy analyses were used to analyse the brain parenchyma, cerebrovasculature, and retinal vessels of mice expressing the disease-causing COL4A1 p.G498V mutation. Mutant mice developed cerebral microhaemorrhages and macroscopic haemorrhages (macrohaemorrhages), the latter with reduced penetrance, mimicking the human disease. Microhaemorrhages that occurred in early postnatal life were associated with a transient, generalized increase in blood-brain barrier permeability at the level of capillaries. Macrohaemorrhages, which occurred later in life, originated from deep brain arteries with focal loss of smooth muscle cells. Similar smooth muscle cell loss was detected in retinal arteries, and a time-course analysis of arterial lesions showed that smooth muscle cells are recruited normally in arterial wall during development, but undergo progressive apoptosis-mediated degeneration. By assessing in parallel the extent of these retinal arterial lesions and the presence/absence of macrohaemorrhages, we found that the arterial lesion load in the retina is strongly correlated with the burden of macrohaemorrhages. We conclude that microhaemorrhages and macrohaemorrhages are driven by two distinct mechanisms. Moreover, smooth muscle cell degeneration is a critical factor underlying the partial penetrance of COL4A1-related macrohaemorrhages, and retinal imaging is a promising tool for identifying high-risk patients. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

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“…For example, the α3(IV), α4(IV), and α5(IV) chains are present in the glomerular basement membrane of the kidney and in the BM of lung, testis, and eye, whereas the α5(IV) and α6(IV) chains are found in the BM of skin, smooth muscle, and the kidney . Most mutations in COL4A1 and COL4A2, the genes encoding α1(IV) or α2(IV), respectively, cause multisystem disorders with heterogeneous pathogenic mechanisms and often lead to embryonic lethality . Mutations in COL4A3, COL4A4, and COL4A5, the genes encoding α3(IV), α4(IV), or α5(IV) chains, respectively, lead to renal failure and deafness in adult patients with Alport's syndrome …”

Section: Introductionmentioning

confidence: 99%

“…9 Most mutations in COL4A1 and COL4A2, the genes encoding a1(IV) or a2(IV), respectively, cause multisystem disorders with heterogeneous pathogenic mechanisms and often lead to embryonic lethality. [10][11][12][13][14] Mutations in COL4A3, COL4A4, and COL4A5, the genes encoding a3(IV), a4(IV), or a5(IV) chains, respectively, lead to renal failure and deafness in adult patients with Alport's syndrome. 15,16 Once secreted into the extracellular space, the triple-helical protomers self-associate to form distinct networks providing a molecular scaffold for interactions between other BM components such as laminin networks, perlecans, and proteoglycans to form a mature BM.…”

Section: Introductionmentioning

confidence: 99%

Building collagen IV smart scaffolds on the outside of cells

Brown

Cummings²,

Vanacore

et al. 2017

Protein Science

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Collagen IV scaffolds assemble through an intricate pathway that begins intracellularly and is completed extracellularly. Multiple intracellular enzymes act in concert to assemble collagen IV protomers, the building blocks of collagen IV scaffolds. After being secreted from cells, protomers are activated to initiate oligomerization, forming insoluble networks that are structurally reinforced with covalent crosslinks. Within these networks, embedded binding sites along the length of the protomer lead to the "decoration" of collagen IV triple helix with numerous functional molecules. We refer to these networks as "smart" scaffolds, which as a component of the basement membrane enable the development and function of multicellular tissues in all animal phyla. In this review, we present key molecular mechanisms that drive the assembly of collagen IV smart scaffolds.

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HANAC Col4a1 Mutation in Mice Leads to Skeletal Muscle Alterations due to a Primary Vascular Defect

Cited by 32 publications

References 33 publications

Bioinformatics analysis suggests that COL4A1 may play an important role in gastric carcinoma recurrence

Bioinformatics analysis suggests that COL4A1 may play an important role in gastric carcinoma recurrence

Severity of arterial defects in the retina correlates with the burden of intracerebral haemorrhage in COL4A1‐related stroke

Building collagen IV smart scaffolds on the outside of cells

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