Variants in LAMC3 Causes Occipital Cortical Malformation

Occipital cortical malformation (OCCM) is a disease caused by malformations of cortical development characterized by polymicrogyria and pachygyria of the occipital lobes and childhood-onset seizures. The recessive or complex heterozygous variants of the LAMC3 gene are identified as the cause of OCCM. In the present study, we identified novel complex heterozygous variants (c.470G > A and c.4030 + 1G > A) of the LAMC3 gene in a Chinese female with childhood-onset seizures. Cranial magnetic resonance imaging was normal. Functional experiments confirmed that both variant sites caused premature truncation of the laminin γ3 chain. Bioinformatics analysis predicted 10 genes interacted with LAMC3 with an interaction score of 0.4 (P value = 1.0e–16). The proteins encoded by these genes were mainly located in the basement membrane and extracellular matrix component. Furthermore, the biological processes and molecular functions from gene ontology analysis indicated that laminin γ3 chain and related proteins played an important role in structural support and cellular processes through protein-containing complex binding and signaling receptor binding. KEGG pathway enrichment predicted that the LAMC3 gene variant was most likely to participate in the occurrence and development of OCCM through extracellular matrix receptor interaction and PI3K-Akt signaling pathway.

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Regulation of the Extracellular Matrix by Ciliary Machinery

Cells ◽

10.3390/cells9020278 ◽

2020 ◽

Vol 9 (2) ◽

pp. 278 ◽

Cited By ~ 3

Author(s):

Collins I ◽

Wann A.K.T

Keyword(s):

Extracellular Matrix ◽

Primary Cilium ◽

Indirect Evidence ◽

Tissue Homeostasis ◽

Cell Behaviour ◽

Structural Support ◽

Cellular Processes ◽

Cellular Signalling ◽

The Matrix

The primary cilium is an organelle involved in cellular signalling. Mutations affecting proteins involved in cilia assembly or function result in diseases known as ciliopathies, which cause a wide variety of phenotypes across multiple tissues. These mutations disrupt various cellular processes, including regulation of the extracellular matrix. The matrix is important for maintaining tissue homeostasis through influencing cell behaviour and providing structural support; therefore, the matrix changes observed in ciliopathies have been implicated in the pathogenesis of these diseases. Whilst many studies have associated the cilium with processes that regulate the matrix, exactly how these matrix changes arise is not well characterised. This review aims to bring together the direct and indirect evidence for ciliary regulation of matrix, in order to summarise the possible mechanisms by which the ciliary machinery could regulate the composition, secretion, remodelling and organisation of the matrix.

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Bioanalytical methods for circulating extracellular matrix-related proteins: new opportunities in cancer diagnosis

Analytical and Bioanalytical Chemistry ◽

10.1007/s00216-021-03416-2 ◽

2021 ◽

Author(s):

Ramón Lorenzo-Gómez ◽

Rebeca Miranda-Castro ◽

Noemí de-los-Santos-Álvarez ◽

María Jesús Lobo-Castañón

Keyword(s):

Extracellular Matrix ◽

Cancer Diagnosis ◽

Bioanalytical Methods ◽

Related Proteins

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Maternal Uterine Vascular Remodeling During Pregnancy

Physiology ◽

10.1152/physiol.00033.2008 ◽

2009 ◽

Vol 24 (1) ◽

pp. 58-71 ◽

Cited By ~ 183

Author(s):

George Osol ◽

Maurizio Mandala

Keyword(s):

Extracellular Matrix ◽

Blood Flow ◽

Vascular Remodeling ◽

Normal Pregnancy ◽

Uterine Blood Flow ◽

Growth And Remodeling ◽

Cellular Mechanisms ◽

Cellular Processes ◽

Uteroplacental Blood Flow ◽

Uterine Circulation

Sufficient uteroplacental blood flow is essential for normal pregnancy outcome and is accomplished by the coordinated growth and remodeling of the entire uterine circulation, as well as the creation of a new fetal vascular organ: the placenta. The process of remodeling involves a number of cellular processes, including hyperplasia and hypertrophy, rearrangement of existing elements, and changes in extracellular matrix. In this review, we provide information on uterine blood flow increases during pregnancy, the influence of placentation type on the distribution of uterine vascular resistance, consideration of the patterns, nature, and extent of maternal uterine vascular remodeling during pregnancy, and what is known about the underlying cellular mechanisms.

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ACTN4 Mediates SEPT14 Mutation-Induced Sperm Head Defects

Biomedicines ◽

10.3390/biomedicines8110518 ◽

2020 ◽

Vol 8 (11) ◽

pp. 518

Author(s):

Yu-Hua Lin ◽

Chia-Yen Huang ◽

Chih-Chun Ke ◽

Ya-Yun Wang ◽

Tsung-Hsuan Lai ◽

...

Keyword(s):

Mass Spectrometry ◽

Cell Model ◽

Membrane Dynamics ◽

Sperm Head ◽

Cellular Processes ◽

Germ Cell Line ◽

Head Formation ◽

Fourth Component ◽

Related Proteins ◽

Cellular Components

Septins (SEPTs) are highly conserved GTP-binding proteins and the fourth component of the cytoskeleton. Polymerized SEPTs participate in the modulation of various cellular processes, such as cytokinesis, cell polarity, and membrane dynamics, through their interactions with microtubules, actin, and other cellular components. The main objective of this study was to dissect the molecular pathological mechanism of SEPT14 mutation-induced sperm head defects. To identify SEPT14 interactors, co-immunoprecipitation (co-IP) and nano-liquid chromatography-mass spectrometry/mass spectrometry were applied. Immunostaining showed that SEPT14 was significantly localized to the manchette structure. The SEPT14 interactors were identified and classified as (1) SEPT-, (2) microtubule-, (3) actin-, and (4) sperm structure-related proteins. One interactor, ACTN4, an actin-holding protein, was selected for further study. Co-IP experiments showed that SEPT14 interacts with ACTN4 in a male germ cell line. SEPT14 also co-localized with ACTN4 in the perinuclear and manchette regions of the sperm head in early elongating spermatids. In the cell model, mutated SEPT14 disturbed the localization pattern of ACTN4. In a clinical aspect, sperm with mutant SEPT14, SEPT14A123T (p.Ala123Thr), and SEPT14I333T (p.Ile333Thr), have mislocalized and fragmented ACTN4 signals. Sperm head defects in donors with SEPT14 mutations are caused by disruption of the functions of ACTN4 and actin during sperm head formation.

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Is There a Relationship Between Psoriasis and Hepatitis C?: a Meta-analysis and Bioinformatics Investigation

10.21203/rs.3.rs-249926/v1 ◽

2021 ◽

Author(s):

Yong Liu ◽

Sheng Nan Cui ◽

Meng Yao Duan ◽

Zhi Li Dou ◽

Yi Zhen Li ◽

...

Keyword(s):

Hepatitis C ◽

Meta Analysis ◽

Enrichment Analysis ◽

Case Control ◽

Cochrane Library ◽

Receptor Interaction ◽

Pathway Enrichment Analysis ◽

Overlapping Genes ◽

Cross Sectional ◽

Pathway Enrichment

Abstract Background: The relationship between psoriasis and hepatitis C was previously controversial, so our purpose is to investigate this connection.Methods: We conducted a systematic review of the case-control, cross-sectional and cohort studies examining the association between psoriasis and hepatitis C in PubMed, EMBASE and Cochrane library databases and investigated the overlapping genes between psoriasis targets and hepatitis C targets using bioinformatics analysis. Based on overlapping genes and hub nodes, we also constructed the protein-protein interaction (PPI) network and module respectively, followed by the pathway enrichment analysis. Results: We included 11 publications that reported a total of 11 studies (8 cross-sectional and 3 case-control). The case–control and cross-sectional studies included 25,047 psoriasis patients and 4,091,631 controls in total. Psoriasis was associated with a significant increase of prevalent hepatitis C (OR 1.72; 95% confidence interval [CI] (1.17-2.52)). A total of 389 significant genes were common to both hepatitis C and psoriasis, which mainly involved IL6, TNF, IL10, ALB, STAT3 and CXCL8. The module and pathway enrichment analyses showed that the common genes had the potential to influence varieties of biological pathways, including the inflammatory response, cytokine activity, cytokine-cytokine receptor interaction, Toll-like receptor signaling pathway, which play an important role in the pathogenesis of hepatitis C and psoriasis.Conclusion: Patients with psoriasis display increased prevalence of hepatitis C and the basic related mechanisms between hepatitis C and psoriasis had been preliminarily clarified.

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Bone Mesenchymal Stem Cells Promote Extracellular Matrix Remodeling of Degenerated Nucleus Pulposus Cells via the miR-101-3p/EIF4G2 Axis

Frontiers in Bioengineering and Biotechnology ◽

10.3389/fbioe.2021.642502 ◽

2021 ◽

Vol 9 ◽

Author(s):

Zeng Wang ◽

Xiaolin Ding ◽

Feifei Cao ◽

Xishan Zhang ◽

Jingguo Wu

Keyword(s):

Extracellular Matrix ◽

Nucleus Pulposus ◽

Quantitative Polymerase Chain Reaction ◽

Matrix Remodeling ◽

Nucleus Pulposus Cells ◽

Promoting Effect ◽

Bone Mesenchymal Stem Cells ◽

Ecm Remodeling ◽

Lumbar Vertebral Fracture ◽

Related Proteins

The etiology of lumbocrural pain is tightly concerned with intervertebral disk degeneration (IDD). Bone mesenchymal stem cell (BMSC)-based therapy bears potentials for IDD treatment. The properties of microRNA (miRNA)-modified BMSCs may be altered. This study investigated the role and mechanism of BMSCs promoting extracellular matrix (ECM) remodeling of degenerated nucleus pulposus cells (NPCs) via the miR-101-3p/EIF4G2 axis. NPCs were collected from patients with IDD and lumbar vertebral fracture (LVF). The expressions of miR-101-3p and ECM-related proteins, Collagen-I (Col-I) and Collagen-II (Col-II), were detected using the reverse transcription-quantitative polymerase chain reaction. The expressions of Col-I and Col-II, major non-collagenous component Aggrecan, and major catabolic factor Matrix metalloproteinase-13 (MMP-13) were detected using Western blotting. BMSCs were cocultured with degenerated NPCs from patients with IDD. Viability and apoptosis of NPCs were measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and flow cytometry. After the degenerated NPCs were transfected with the miR-101-3p inhibitor, the expressions of ECM-related proteins, cell viability, and apoptosis were detected. The targeting relationship between miR-101-3p and EIF4G2 was verified. Functional rescue experiments verified the effects of miR-101-3p and EIF4G2 on ECM remodeling of NPCs. Compared with the NPCs of patients with LVF, the degenerated NPCs of patients with IDD showed downregulated miR-101-3p, Col-II, and Aggrecan expressions and upregulated MMP-13 and Col-I expressions. BMSCs increased the expressions of miR-101-3p, Aggrecan, and Col-II, and decreased the expressions of MMP-13 and Col-I in degenerated NPCs. BMSCs enhanced NPC viability and repressed apoptosis. Downregulation of miR-101-3p suppressed the promoting effect of BMSCs on ECM remodeling. miR-101-3p targeted EIF4G2. Downregulation of EIF4G2 reversed the inhibiting effect of the miR-101-3p inhibitor on ECM remodeling. In conclusion, BMSCs increased the miR-101-3p expression in degenerated NPCs to target EIF4G2, thus promoting the ECM remodeling of NPCs.

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Long Noncoding RNA CTD-2589M5.4 Inhibits Ovarian Cancer Cell Proliferation, Migration, and Invasion Via Downregulation of the Extracellular Matrix–Receptor Interaction Pathway

Cancer Biotherapy & Radiopharmaceuticals ◽

10.1089/cbr.2020.4429 ◽

2021 ◽

Author(s):

Yuanyuan Gu ◽

Ke Huang ◽

Min Zhang ◽

Fang Teng ◽

Lili Ge ◽

...

Keyword(s):

Ovarian Cancer ◽

Extracellular Matrix ◽

Cell Proliferation ◽

Cancer Cell ◽

Long Noncoding Rna ◽

Noncoding Rna ◽

Ovarian Cancer Cell ◽

Migration And Invasion ◽

Receptor Interaction ◽

Cancer Cell Proliferation

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Transcriptomic analysis of Procambarus clarkii affected by “Black May” disease

Scientific Reports ◽

10.1038/s41598-020-78191-8 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Guoqing Shen ◽

Xiao Zhang ◽

Jie Gong ◽

Yang Wang ◽

Pengdan Huang ◽

...

Keyword(s):

Procambarus Clarkii ◽

Kegg Pathway ◽

Enrichment Analysis ◽

Differentially Expressed ◽

Pathway Enrichment Analysis ◽

Apoptosis Pathway ◽

Pathway Enrichment ◽

Cellular Processes ◽

Expression Of Genes ◽

Muscle Tissues

AbstractEach year from April to May, high mortality rates are reported in red swamp crayfish (Procambarus clarkii) cultured in Jiangsu and other regions, in China, and this phenomenon has come to be known as “Black May” disease (BMD). Therefore, in order to investigate the possible causes of this disease, this study gathered BMD-affected P. clarkii samples and performed transcriptome analysis on hepatopancreas, gill, and muscle tissues. A total of 19,995,164, 149,212,804, and 222,053,848 clean reads were respectively obtained from the gills, muscle, and hepatopancreas of BMD-affected P. clarkii, and 114,024 unigenes were identified. The number of differentially expressed genes (DEGs) in gill, muscle, and hepatopancreas was 1703, 964, and 476, respectively. GO and KEGG enrichment analyses of the DEGs were then conducted. Based on KEGG pathway enrichment analysis, the most significantly differentially expressed pathways were mainly those involved with metabolism, human disease, and cellular processes. Further analysis of the significantly DEGs revealed that they were mainly related to the mitochondrial-mediated apoptosis pathway and that the expression of these DEGs was mostly down-regulated. Moreover, the expression of genes related to immune and metabolism-related pathways was also significantly down-regulated, and these significantly-inhibited pathways were the likely causes of P. clarkii death. Therefore, our results provide a basis for the identification of BMD causes.

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Discovery of crucial cytokines associated with abdominal aortic aneurysm formation by protein array analysis

Experimental Biology and Medicine ◽

10.1177/1535370219885101 ◽

2019 ◽

Vol 244 (18) ◽

pp. 1648-1657

Author(s):

Yuan Li ◽

Dan Yang ◽

Bo Sun ◽

Xu Zhang ◽

Fangda Li ◽

...

Keyword(s):

Abdominal Aortic Aneurysm ◽

Aortic Aneurysm ◽

Cathepsin L ◽

Enrichment Analysis ◽

Differentially Expressed ◽

Antibody Array ◽

Pathway Enrichment Analysis ◽

Pathway Enrichment ◽

Abdominal Aortic ◽

Related Proteins

As a common disease, abdominal aortic aneurysm (AAA) features permanently progressively dilated abdominal aorta. Various cytokines are implicated in AAA pathogenesis. Clarification of involved cytokines combined with functional analysis may provide new insights into AAA pathogenesis. Using a mouse model, this study analyzed the cytokine profiles in AAA. Cytokines were measured in AAA tissues of saline control or angiotensin II-treated ApoE−/− mice using an antibody array of 200 cytokines, cytokine receptors, and related proteins. Statistical analysis revealed that 21 of 200 proteins were differentially expressed in AAA. These differentially expressed proteins were subjected to function and pathway enrichment analysis, which revealed that leukocyte migration and positive regulation of cell adhesion were the most significant biological processes. Specific signaling pathways, including Janus kinase/signal transducers and activators of transcription and cytokine–cytokine receptor interaction, were prominent in Kyoto encyclopedia of genes and genomes pathway enrichment analysis. Importantly, our data identified cytokines which had not previously been illustrated in AAA pathogenic pathways. Bivariate correlation analysis between these cytokines and protease activity showed that granulocyte colony-stimulating factor (G-CSF), macrophage inflammatory protein 1 g, cardiotrophin 1, milk fat globule-EGF factor 8 protein, interleukin 33, and periostin were positively correlated with matrix metalloprotease 1 (MMP-1), MMP-9, cathepsin B, and cathepsin L. G-CSF was positively correlated with cathepsin L. In conclusion, these results demonstrate that cytokine profile is significantly altered in AAA, and that the newly identified crucial cytokines may function potentially in AAA pathogenesis. Impact statement Various cytokines are known contributors to abdominal aortic aneurysm (AAA) pathologic processes, but the mechanisms underlying the pathogenesis remains unclear. We illustrated the altered cytokine profiles in AAA by high throughput antibody array of 200 cytokines, cytokine receptors and related proteins, as well as bioinformatics analysis of differentially expressed proteins in lesion tissues from AAA mice infused with angiotensin II. Functional analyses of differentially expressed cytokines showed clustering on cell migration and adhesion processes. More importantly, crucial cytokines whose association with AAA formation had not been established were identified. Significant correlations were found between these cytokines and protease activity. This study identifies several crucial markers for further researches on the molecular basis of AAA.

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