scholarly journals Profiling extra cellular matrix associated proteome of human fetal nucleus pulposus in search for regenerative targets

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shanmuganathan Rajasekaran ◽  
Chitra Thangavel ◽  
Niek Djuric ◽  
Muthurajan Raveendran ◽  
Dilip Chand Raja Soundararajan ◽  
...  

AbstractDegeneration of the intervertebral disc is associated with a decrease in extra-cellular matrix (ECM) content due to an imbalance in anabolic and catabolic signaling. Our previous study profiled the core matrisome of fetal NP’s and identified various proteins with anabolic potential for regenerative therapies. This study aims to complement those results by exploring ECM regulators, associated proteins and secreted factors of the fetal nucleus pulposus (NP). Proteomic data of 9 fetal, 7 healthy adults (age 22–79), and 11 degenerated NP’s was analyzed. Based on the selection criteria, a total of 45 proteins were identified, of which 14 were uniquely expressed or upregulated in fetus compared to adult NP’s. Pathway analysis with these proteins revealed a significant upregulation of one pathway and two biological processes, in which 12 proteins were involved. Prolyl 4 hydroxylase (P4HA) 1 and 2, Procollagen-lysine, 2-oxoglutarate 5-dioxygenase (PLOD) 1, and Heat shock protein 47 (SERPINH1) were involved in ‘collagen biosynthesis’ pathway. In addition, PLOD 1, SERPINH1, Annexin A1 and A4, CD109 and Galectin 3 (LGALS3) were all involved in biological process of ‘tissue development’. Furthermore Annexin A1, A4 and A5, LGALS-3 and SERPINF1 were featured in ‘negative regulation of cell death’. In conclusion, additionally to core ECM proteome, this study reveals ECM regulators and ECM affiliated proteins of interest to study for regenerative therapies, and their potential should be validated in future mechanistic experiments.

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Shanmuganathan Rajasekaran ◽  
Chitraa Tangavel ◽  
Niek Djuric ◽  
Muthurajan Raveendran ◽  
Dilip Chand Raja Soundararajan ◽  
...  

Abstract Intervertebral disc degeneration is accompanied by a loss of Extra-cellular matrix (ECM) due to an imbalance in anabolic and catabolic pathways. Identifying ECM proteins with anabolic and/or regenerative potential could be the key to developing regenerative therapies. Since human fetal discs grow and develop rapidly, studying these discs may provide valuable insights on proteins with regenerative potential. This study compares core matrisome of 9 fetal and 7 healthy adult (age 22–79) nucleus pulposus (NP), using a proteomic and bioinformatic approach. Of the 33 upregulated proteins in fetus NP’s, 20 of which were involved in ECM assembly pathways: fibromodulin, biglycan, heparan sulfate proteoglycan 2, chondroitin sulfate proteoglycan 4, procollagen C-endopeptidase enhancer and Collagen—type 1a1, 1a2, 6a1, 6a3, 11a1, 11a2, 12a1, 14a1 and 15a1. Moreover, 10 of the upregulated proteins were involved in growth pathways ‘PI3L-Akt signaling’ and ‘regulation of insulin like growth factor transport and uptake.’ Thrombospondin 1,3 and 4, tenascin C, matrilin-3, and collagen- type 1a1, 1a2, 6a1, 6a3 and 9a1. Additionally, matrillin-2 and ‘Collagen triple helix repeat containing 1’ were identified as possible regenerative proteins due to their involvement in ‘Regeneration’ and ‘tissue development’ respectively. In conclusion, the consistency of human fetal NP’s differs greatly from that of healthy adults. In view of these outcomes, the core matrisome of human fetal discs contains an abundant number of proteins that could potentially show regenerative properties, and their potential should be explored in future machinal experiments.


2011 ◽  
Vol 59 (S 01) ◽  
Author(s):  
M Franz ◽  
A Berndt ◽  
K Grün ◽  
D Neri ◽  
H Kosmehl ◽  
...  

2004 ◽  
Vol 1 (4) ◽  
pp. 368-371
Author(s):  
Gianluigi Giannelli ◽  
Concetta Sgarra ◽  
Caterina Foti ◽  
Carlo Bergamini ◽  
Carmela Coviello ◽  
...  

Author(s):  
Hariharan Jayaraman ◽  
Nalinkanth V. Ghone ◽  
Ranjith Kumaran R ◽  
Himanshu Dashora

: Mesenchymal stem cells because of its high proliferation, differentiation, regenerative capacity, and ease of availability have been a popular choice in cytotherapy. Mesenchymal Stem Cells (MSCs) have a natural tendency to home in a tumor microenvironment and acts against it, owing to the similarity of the latter to an injured tissue environment. Several studies have confirmed the recruitment of MSCs by tumor through various cytokine signaling that brings about phenotypic changes to cancer cells, thereby promoting migration, invasion, and adhesion of cancer cells. The contrasting results on MSCs as a tool for cancer cytotherapy may be due to the complex cell to cell interaction in the tumor microenvironment, which involves various cell types such as cancer cells, immune cells, endothelial cells, and cancer stem cells. Cell to cell communication can be simple or complex and it is transmitted through various cytokines among multiple cell phenotypes, mechano-elasticity of the extra-cellular matrix surrounding the cancer cells, and hypoxic environments. In this article, the role of the extra-cellular matrix proteins and soluble mediators that acts as communicators between mesenchymal stem cells and cancer cells has been reviewed specifically for breast cancer, as it is the leading member of cancer malignancies. The comprehensive information may be beneficial in finding a new combinatorial cytotherapeutic strategy using MSCs by exploiting the cross-talk between mesenchymal stem cells and cancer cells for treating breast cancer.


BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Giuliana Cavalloni ◽  
Caterina Peraldo-Neia ◽  
Annamaria Massa ◽  
Carlo Bergamini ◽  
Alessandro Trentini ◽  
...  

Abstract Background Cholangiocarcinoma (CCA) is an aggressive disease with poor prognosis. A molecular classification based on mutational, methylation and transcriptomic features could allow identifying tailored therapies to improve CCA patient outcome. Proteomic remains partially unexplored; here, we analyzed the proteomic profile of five intrahepatic cholangiocarcinoma (ICC) derived from Italian patients undergone surgery and one normal bile duct cell line. Methods Proteome profile was investigated by using 2D electrophoresis followed by Mass Spectrometry (MS). To validate proteomic data, the expression of four overexpressed proteins (CAT, SOD, PRDX6, DBI/ACBP) was evaluated by immunohistochemistry in an independent cohort of formalin fixed, paraffin-embedded (FFPE) ICC tissues. We also compared proteomic data with those obtained by transcriptomic profile evaluated by microarray analysis of the same tissues. Results We identified 19 differentially expressed protein spots, which were further characterized by MS; 13 of them were up- and 6 were down-regulated in ICC. These proteins are mainly involved in redox processes (CAT, SODM, PRDX2, PRDX6), in metabolism (ACBP, ACY1, UCRI, FTCD, HCMS2), and cell structure and organization (TUB2, ACTB). CAT is overexpressed in 86% of patients, PRDX6 in 73%, SODM in 100%, and DBI/ACBP in 81% compared to normal adjacent tissues. A concordance of 50% between proteomic and transcriptomic data was observed. Conclusions This study pointed out that the impairment of the metabolic and antioxidant systems, with a subsequent accumulation of free radicals, might be a key step in CCA development and progression.


Author(s):  
İREM ÇAY ◽  
SERDAL PAMUK

In this work, we obtain the numerical solutions of a 2D mathematical model of tumor angiogenesis originally presented in [Pamuk S, ÇAY İ, Sazci A, A 2D mathematical model for tumor angiogenesis: The roles of certain cells in the extra cellular matrix, Math Biosci 306:32–48, 2018] to numerically prove that the certain cells, the endothelials (EC), pericytes (PC) and macrophages (MC) follow the trails of the diffusions of some chemicals in the extracellular matrix (ECM) which is, in fact, inhomogeneous. This leads to branching, the sprouting of a new neovessel from an existing vessel. Therefore, anastomosis occurs between these sprouts. In our figures we do see these branching and anastomosis, which show the fact that the cells diffuse according to the structure of the ECM. As a result, one sees that our results are in good agreement with the biological facts about the movements of certain cells in the Matrix.


2018 ◽  
Vol 9 (1) ◽  
pp. 1-13 ◽  
Author(s):  
Clive J. Curley ◽  
Eimear B. Dolan ◽  
Matthias Otten ◽  
Svenja Hinderer ◽  
Garry P. Duffy ◽  
...  

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