scholarly journals High expression of COL5A2, a member of COL5 family, indicates the poor survival and facilitate cell migration in gastric cancer

2021 ◽  
Author(s):  
Yuen Tan ◽  
Qingchuan Chen ◽  
Xing Yao ◽  
Chao Zhang ◽  
Siwei Pan ◽  
...  

Background Gastric cancer (GC) metastasis determines the prognosis of patients, and exploring the molecular mechanism of GC metastasis is expected to provide a theoretical basis for clinical treatment. Recent studies have shown that extracellular matrix protein is closely related to GC metastasis. This study aimed to explore the expression profile and role of COL5A2, as an extracellular matrix protein, in GC.  Methods The expression, overall survival and progression-free survival data of COL5 family members were extracted from The Cancer Genome Atlas(TCGA)database, respectively. Weighted gene co-expression network analysis of the GSE62229 database was performed out to identify modules and associated genes.</p>  Results COL5A2 was selected as our research target in the TCGA database, and was also verified in the GSE62229 and GSE15459 datasets. COL5A2 was upregulated in GC tissues by paraffin immunohistochemistry and RT-qPCR. The prognosis of patients with low COL5A2 expression was better than that of patients with high COL5A2 expression. Scratch and migration experiments showed that knockdown of COL5A2 decreased the migration ability of gastric cancer cells compared with the control group. In vivo, mice with tail vein injection COL5A2 knockdown had fewer and smaller metastatic nodules in liver. GSEA results showed that the TCGA and GSE62229 samples were significantly enriched in several well-known cancer-related pathways, such as the TGF-β, MAPK, and JAK2 signaling pathways.</p>  Conclusion COL5A2 was most closely related to advanced GC among COL5 family members. High COL5A2 expression is associated with a poor prognosis, and may be a novel therapeutic target for GC.

2020 ◽  
Author(s):  
Yu-en Tan ◽  
Qing-chuan Chen ◽  
Yao Xing ◽  
Chao Zhang ◽  
Si-wei Pan ◽  
...  

Abstract Background Gastric cancer (GC) metastasis determines the prognosis of patients, and exploring the molecular mechanism of GC metastasis is expected to provide a theoretical basis for clinical treatment. Recent studies have shown that extracellular matrix protein is closely related to GC metastasis. This study aimed to explore the expression profile and role of COL5A2 (Collagen V-type α2), as an extracellular matrix protein, in GC. Methods The expression, overall survival and progression-free survival data of COL5 family members were extracted from The Cancer Genome Atlas(TCGA)database, respectively. Paraffin immunohistochemistry and RT-qPCR in GC and matched normal tissues were used to analyze the expression of the target genes. Weighted gene co-expression network analysis of the GSE62229 database was performed out to identify modules and associated genes, and the functions were predicted by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Results COL5A2 was selected as our research target in the TCGA database, and was also verified in the GSE62229 and GSE15459 datasets. COL5A2 was upregulated in GC tissues by paraffin immunohistochemistry and RT-qPCR. The analysis of clinicopathological characteristics showed a significant difference in the Borrmann type (P = 0.036), histological type (P = 0.013) and T stage(P = 0.011). The prognosis of patients with low COL5A2 expression was better than that of patients with high COL5A2 expression. GSEA results showed that the TCGA and GSE62229 samples were significantly enriched in several well-known cancer-related pathways, such as the TGF-β, MAPK, and JAK2 signaling pathways. Conclusion COL5A2 was most closely related to advanced GC among COL5 family members. High COL5A2 expression is associated with a poor prognosis in GC, and may be a novel therapeutic target for GC.


2020 ◽  
Vol 10 (4) ◽  
pp. 257-265
Author(s):  
Sonat Pınar Kara ◽  
Gülsüm Özkan ◽  
Demet Özkaramanlı Gür ◽  
Gaye Kübra Emeksiz ◽  
Ahsen Yılmaz ◽  
...  

Introduction: Chronic kidney disease (CKD) is a widespread health problem, in which mortality is most frequently due to cardiovascular diseases. Microfibrillar-associated protein 4 (MFAP4) is an extracellular matrix protein. MFAP4 is involved in several biological processes, particularly the maintenance of vascular integrity and extracellular matrix remodeling. Our review of the literature revealed no data concerning MFAP4 levels in CKD and its relationship with myocardial functions. Objective:The purpose of this study was therefore to investigate MFAP4 levels in CKD, parameters affecting these, and the relationship with myocardial functions. Materials and Methods: Seventy-nine CKD patients and 30 healthy controls were included in the study. Routine biochemical tests and echocardiography were performed once demographic data had been recorded. Blood specimens were collected for MFAP4 analysis, and the results were subjected to statistical analysis. Results: MFAP4 levels were significantly higher in the patient group than in the control group (p< 0.001). Doppler parameters revealed more frequent LV diastolic impairment in the patient group. Tissue Doppler systolic velocity and global longitudinal strain were significantly impaired, revealing the subclinical LV systolic dysfunction in CKD patients. MFAP4 elevation in the patient group was positively correlated with aortic root (AR), global circumferential strain (GCS), and GCS rate. Conclusion: Our results showed MFAP4 elevation in CKD for the first time in the literature, and that this elevation may be related to GCS and AR dilation. We think that, once supported by further studies, MFAP4 may constitute a marker in the evaluation of myocardial functions in CKD.


2005 ◽  
Vol 18 (6) ◽  
pp. 727-731 ◽  
Author(s):  
Cidônia de Lourdes Vituri ◽  
Márcio Alvarez-Silva ◽  
Andréa Gonçalves Trentin ◽  
Vera Lúcia Cardoso Garcia Tramonte ◽  
Primavera Borelli

OBJECTIVE: The objective of the present study was to measure the concentration of bone marrow extracellular matrix thrombospondin in mice, following hypoplasia induced by protein malnutrition. METHODS: Two-month-old male Swiss mice were submitted to protein malnutrition by way of a low-protein diet containing 4.0% casein until they lost 20.0% of their original body weight, while the control group mice were fed 14.0% casein for 15 days. The bone marrows of the animals were aspirated and transferred to phosphate-buffered saline tubes for extraction. The extracellular matrix protein was analyzed by 7.5% SDS-PAGE and thrombospondin by Enhanced Chemiluminescence Light Western blotting. RESULTS: The amount of thrombospondin was 30% higher in the undernourished samples when compared to the control samples. CONCLUSION: This study suggests that the hypoplasia induced by protein malnutrition probably alters the functioning of the bone marrow microenvironment resulting in a higher thrombospondin concentration.


2018 ◽  
Vol 38 (2) ◽  
pp. 255-266 ◽  
Author(s):  
M Sözmen ◽  
AK Devrim ◽  
YB Kabak ◽  
T Devrim

Periostin is an extracellular matrix protein from the fasciclin family that guides cellular trafficking and extracellular matrix organization. Periostin stimulates mature cardiomyocytes to reenter the cell cycle. The molecular mechanism behind such stimulation remains to be explored. A DNA microarray technology constituting 30,429 gene-level probe sets was utilized to investigate effects of recombinant murine periostin peptide on the gene expression pattern in a rat model of isoproterenol (ISO)-induced myocardial injury. The experiment was performed on 84 adult male Sprague-Dawley rats in four groups ( n = 21): (1) control group, (2) only periostin applied group, (3) ISO cardiotoxicity group, and (4) ISO + periostin group. The experiment was continued for 28 days, and rats were killed on days 1, 7, and 28 ( n = 7). Microarray analyses revealed that periostin significantly altered the expression of at least ±2-fold of 2474 genes in the ISO + periostin group compared to the ISO cardiotoxicity group of which 521 genes altered out of 30,429 gene-level probe sets. Ingenuity pathway analysis indicated that multiple pathway networks were affected by periostin, with predominant changes occurring in the expression of genes involved in oxidative phosphorylation, oxidative stress, fatty acid metabolism, and TNF-α NF-κB signaling pathways. These findings indicate that periostin alters gene expression profile in the ISO-induced myocardial injury and modulates local myocardial inflammation, possibly mitigating inflammation through TNF-α NF-κB signaling pathway along with a decreased Casp7 activity and apoptotic cell death.


2007 ◽  
Vol 177 (4S) ◽  
pp. 421-422
Author(s):  
Ganka Nikolova ◽  
Christian O. Twiss ◽  
Hane Lee ◽  
Nelson Stanley ◽  
Janet Sinsheimer ◽  
...  

Author(s):  
Aniel Moya-Torres ◽  
Monika Gupta ◽  
Fabian Heide ◽  
Natalie Krahn ◽  
Scott Legare ◽  
...  

Abstract The production of recombinant proteins for functional and biophysical studies, especially in the field of structural determination, still represents a challenge as high quality and quantities are needed to adequately perform experiments. This is in part solved by optimizing protein constructs and expression conditions to maximize the yields in regular flask expression systems. Still, work flow and effort can be substantial with no guarantee to obtain improvements. This study presents a combination of workflows that can be used to dramatically increase protein production and improve processing results, specifically for the extracellular matrix protein Netrin-1. This proteoglycan is an axon guidance cue which interacts with various receptors to initiate downstream signaling cascades affecting cell differentiation, proliferation, metabolism, and survival. We were able to produce large glycoprotein quantities in mammalian cells, which were engineered for protein overexpression and secretion into the media using the controlled environment provided by a hollow fiber bioreactor. Close monitoring of the internal bioreactor conditions allowed for stable production over an extended period of time. In addition to this, Netrin-1 concentrations were monitored in expression media through biolayer interferometry which allowed us to increase Netrin-1 media concentrations tenfold over our current flask systems while preserving excellent protein quality and in solution behavior. Our particular combination of genetic engineering, cell culture system, protein purification, and biophysical characterization permitted us to establish an efficient and continuous production of high-quality protein suitable for structural biology studies that can be translated to various biological systems. Key points • Hollow fiber bioreactor produces substantial yields of homogenous Netrin-1 • Biolayer interferometry allows target protein quantitation in expression media • High production yields in the bioreactor do not impair Netrin-1 proteoglycan quality Graphical abstract


2002 ◽  
Vol 267 (4) ◽  
pp. 440-446 ◽  
Author(s):  
A. Kapetanopoulos ◽  
F. Fresser ◽  
G. Millonig ◽  
Y. Shaul ◽  
G. Baier ◽  
...  

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