scholarly journals T-614 Promotes Osteoblastic Cell Differentiation by Increasing Dlx5 Expression and Regulating the Activation of p38 and NF-κB

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Jinglue Song ◽  
Hongli Liu ◽  
Qi Zhu ◽  
Yutong Miao ◽  
Feiyan Wang ◽  
...  
Keyword(s):  
Ectopic Expression ◽  
Bone Destruction ◽  
Collagen Type I ◽  
Inhibitory Effect ◽  
Osteoblastic Differentiation ◽  
Nodule Formation ◽  
Osteoblastic Cell ◽  
Type I ◽  
Autoimmune Inflammatory Disease

Rheumatoid arthritis (RA) is an autoimmune inflammatory disease characterized by bone loss. Degree of inflammation has been identified as an important initiator of skeletal damage in RA. Iguratimod (T-614) is an anti-inflammatory agent which has been reported to show the inhibitory effect of bone destruction in RA. However, the role of T-614 in osteoblast differentiation is still not clear. In this study, we intended to find the effect of T-614 on the osteogenesis process. We detected osteogenesis markers and transcription factors associated with osteoblastic lineage and bone formation in the culture of mesenchymal stem cells which differentiate osteoblast. The contents and activity of alkaline phosphatase, levels of collagen type I and bone gla protein, and calcium nodule formation were increased significantly after T-614 treated. Meanwhile, the mRNAs expressions of Osterix and Dlx5 were also found to be increased significantly by real-time PCR. The changes of levels of phosphorylation of p38 and NF-κB were also detected by Western blot. The results showed that T-614 promotes osteoblastic differentiation by increasing the expression of Osterix and Dlx5 and increasing the activation of P38. T-614 could advance the ectopic expression of NF-κB to suppress inflammation, which indirectly inhibits the damage of the osteoblasts.

scholarly journals Role of Curing Temperature of Poly(Glycerol Sebacate) Substrates on Protein-Cell Interaction and Early Cell Adhesion

Polymers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 382
Author(s):  
Rubén Martín-Cabezuelo ◽  
José Carlos Rodríguez-Hernández ◽  
Guillermo Vilariño-Feltrer ◽  
Ana Vallés-Lluch
Keyword(s):  
Protein Interactions ◽  
Chemical Properties ◽  
Focal Adhesions ◽  
Collagen Type I ◽  
Inhibitory Effect ◽  
Synthesis Temperature ◽  
Curing Temperature ◽  
Cell Protein ◽  
Preliminary Treatment ◽  
Type I

A novel procedure to obtain smooth, continuous polymeric surfaces from poly(glycerol sebacate) (PGS) has been developed with the spin-coating technique. This method proves useful for separating the effect of the chemistry and morphology of the networks (that can be obtained by varying the synthesis parameters) on cell-protein-substrate interactions from that of structural variables. Solutions of the PGS pre-polymer can be spin-coated, to then be cured. Curing under variable temperatures has been shown to lead to PGS networks with different chemical properties and topographies, conditioning their use as a biomaterial. Particularly, higher synthesis temperatures yield denser networks with fewer polar terminal groups available on the surface. Material-protein interactions were characterised by using extracellular matrix proteins such as fibronectin (Fn) and collagen type I (Col I), to unveil the biological interface profile of PGS substrates. To that end, atomic force microscopy (AFM) images and quantification of protein adsorbed in single, sequential and competitive protein incubations were used. Results reveal that Fn is adsorbed in the form of clusters, while Col I forms a characteristic fibrillar network. Fn has an inhibitory effect when incubated prior to Col I. Human umbilical endothelial cells (HUVECs) were also cultured on PGS surfaces to reveal the effect of synthesis temperature on cell behaviour. To this effect, early focal adhesions (FAs) were analysed using immunofluorescence techniques. In light of the results, 130 °C seems to be the optimal curing temperature since a preliminary treatment with Col I or a Fn:Col I solution facilitates the formation of early focal adhesions and growth of HUVECs.

scholarly journals WNT-5A regulates TGF-β-related activities in liver fibrosis

2017 ◽  
Vol 312 (3) ◽  
pp. G219-G227 ◽  
Author(s):  
Leonie Beljaars ◽  
Sara Daliri ◽  
Christa Dijkhuizen ◽  
Klaas Poelstra ◽  
Reinoud Gosens
Keyword(s):  
Liver Fibrosis ◽  
Functional Role ◽  
Collagen Type ◽  
Collagen Type I ◽  
Matrix Proteins ◽  
Type I ◽  
Human Livers

WNT-5A is a secreted growth factor that belongs to the noncanonical members of the Wingless-related MMTV-integration family. Previous studies pointed to a connection between WNT-5A and the fibrogenic factor TGF-β warranting further studies into the functional role of WNT-5A in liver fibrosis. Therefore, we studied WNT-5A expressions in mouse and human fibrotic livers and examined the relation between WNT-5A and various fibrosis-associated growth factors, cytokines, and extracellular matrix proteins. WNT-5A gene and protein expressions were significantly increased in fibrotic mouse and human livers compared with healthy livers. Regression or therapeutic intervention in mice resulted in decreased hepatic WNT-5A levels paralleled by lower collagen levels. Immunohistochemical analysis showed WNT-5A staining in fibrotic septa colocalizing with desmin staining indicating WNT-5A expression in myofibroblasts. In vitro studies confirmed WNT-5A expression in this cell type and showed that TGF-β significantly enhanced WNT-5A expression in contrast to PDGF-BB and proinflammatory cytokines IL-1β and TNF-α. Additionally, TGF-β induces the expression of the WNT receptors FZD2 and FZD8. After silencing of WNT-5A, reduced levels of collagen type I, vimentin, and fibronectin in TGF-β-stimulated myofibroblasts were measured compared with nonsilencing siRNA-treated controls. Interestingly, the antifibrotic cytokine IFNγ suppressed WNT-5A in vitro and in vivo. IFNγ-treated fibrotic mice showed significantly less WNT-5A expression compared with untreated fibrotic mice. In conclusion, WNT-5A paralleled collagen I levels in fibrotic mouse and human livers. WNT-5A expression in myofibroblasts is induced by the profibrotic factor TGF-β and plays an important role in TGF-β-induced regulation of fibrotic matrix proteins, whereas its expression can be reversed upon treatment, both in vitro and in vivo. NEW & NOTEWORTHY This study describes the localization and functional role of WNT-5A in human and mouse fibrotic livers. Hepatic WNT-5A expression parallels collagen type I expression. In vivo and in vitro, the myofibroblasts were identified as the key hepatic cells producing WNT-5A. WNT-5A is under control of TGF-β and its activities are primarily profibrotic.

Role of catechin on collagen type I stability upon oxidation: a NMR approach

2019 ◽  
Vol 34 (1) ◽  
pp. 53-62 ◽  
Author(s):  
Massimo Lucarini ◽  
Fabio Sciubba ◽  
Donatella Capitani ◽  
Maria Enrica Di Cocco ◽  
Laura D’Evoli ◽  
...  
Keyword(s):  
Collagen Type ◽  
Collagen Type I ◽  
Type I

Blockade of hypoxia-reoxygenation-mediated collagen type I expression and MMP activity by overexpression of TGF-β1delivered by AAV in mouse cardiomyocytes

2007 ◽  
Vol 293 (3) ◽  
pp. H1833-H1838 ◽  
Author(s):  
Chang-Ping Hu ◽  
Abhijit Dandapat ◽  
Yong Liu ◽  
Paul L. Hermonat ◽  
Jawahar L. Mehta
Keyword(s):  
Cardiac Remodeling ◽  
Collagen Type ◽  
Transforming Growth Factor ◽  
Collagen Type I ◽  
Type I ◽  
Antioxidant Mechanism ◽  
Multifunctional Peptides ◽  
Expression And Activity ◽  
Hypoxia Reoxygenation

Transforming growth factor (TGF)-β1is one of the most pleiotropic and multifunctional peptides known. While the cardioprotective effect of TGF-β1during ischemia is well known, the specific role of TGF-β1in altering the cardiac remodeling process remains unclear. This study was designed to examine the regulation of hypoxia-reoxygenation-mediated collagen type I expression and activity of matrix metalloproteinases (MMPs) by overexpression of TGF-β1in cultured HL-1 mouse cardiomyocytes. TGF-β1was overexpressed in cardiomyocytes by transfection with adeno-associated virus (AAV)/TGF-β1Latentor with AAV/TGF-β1ACT(active TGF-β1). Twenty-four hours of hypoxia followed by 3 h of reoxygenation (H-R) markedly enhanced (pro)collagen type I expression and activity of MMPs concomitant with an increase in reactive oxygen species (ROS) release and LOX-1 expression. Overexpression of TGF-β1reduced these alterations induced by H-R. TGF-β1overexpression also blocked H-R-mediated p38 and p44/42 MAPK activation. Transfection with AAV/TGF-β1ACTwas superior to that with AAV/TGF-β1Latent. These data for the first time demonstrate that H-R induces signals for cardiac remodeling in cardiomyocytes and TGF-β1can modulate, possibly via antioxidant mechanism, these signals. These findings contribute to further understanding of the role of TGF-β1in the cardiac remodeling process.

The role of collagen type I α2 polymorphisms: intracranial aneurysms in Koreans

2009 ◽  
Vol 72 (1) ◽  
pp. 48-53 ◽  
Author(s):  
Sung-Pil Joo ◽  
Tae-Sun Kim ◽  
Il-Kwon Lee ◽  
Jung-Kil Lee ◽  
Bo-Ra Seo ◽  
...  
Keyword(s):  
Intracranial Aneurysms ◽  
Collagen Type ◽  
Collagen Type I ◽  
Type I

scholarly journals Mechanisms of development of alcohol-dependant osteoporosis

2012 ◽  
Vol 93 (1) ◽  
pp. 120-122
Author(s):  
D N Goryachev ◽  
L R Mukhamedzhanova
Keyword(s):  
Mutual Influence ◽  
Organic Matrix ◽  
Collagen Type I ◽  
Published Data ◽  
Type I ◽  
Characteristic Features ◽  
Chronic Ethanol Intoxication ◽  
Immune Pathology ◽  
Mechanisms Of Development

Presented were the current published data on the mutual influence of different factors on the initiation and progression of disorders of formation of the bone organic matrix and its mineralization during chronic ethanol intoxication. Emphasized was the role of the toxic effect of ethanol on the osteoblastic cells, which is expressed in the increasing viscosity of the cytoplasm, disruption of the architectonics of the cytoplasmic membrane, disorganization of the polyribosomal complexes and reduction of the collagen synthesis functions. Established was the role of immune pathology, which included the formation of antibodies to a number of autogenous tissues. Found were antibodies to collagen type I, which was modified by acetaldehyde and possessed cytotoxicity. In patients with alcohol dependence noted was an increase in the concentration of interleukin-6, which stimulates the early stages of hematopoiesis and osteoclastogenesis. The mechanism of development of alcohol-dependant osteoporosis is understood as a cascade of related processes, which are linked in the circulus vitiosus. Only the initial stages of this cascade have certain specificity. The morphological consequences are mostly similar and do not differ from those of other forms of secondary systemic osteoporosis, however give the characteristic features to the clinical course.

scholarly journals Discoidin Domain Receptor 2 regulates AT1 receptor expression in Angiotensin II-stimulated cardiac fibroblasts via fibronectin-dependent Integrin-β1 signalling

2021 ◽  
Author(s):  
Allen Sam Titus ◽  
Harikrishnan V ◽  
Mingyi Wang ◽  
Edward G Lakkatta ◽  
Shivakumar Kailasam
Keyword(s):  
Angiotensin Ii ◽  
Collagen Type ◽  
Cardiac Fibroblasts ◽  
Collagen Type I ◽  
Cardiac Fibroblast ◽  
Regulatory Role ◽  
Type I ◽  
Integrin Β1 ◽  
Fibronectin Expression

Fibronectin is an extracellular matrix glycoprotein with a regulatory role in fundamental cellular processes. Recent reports on the cardioprotective effect of fibronectin inhibition in a setting of myocardial injury suggest a role for fibronectin in cardiac fibroblast function, which remains largely unexplored. This study probed the molecular basis and functional implications of fibronectin gene expression in cardiac fibroblasts exposed to Angiotensin II, a potent pro-fibrotic factor in the myocardium. Using gene knockdown and over-expression approaches, western blotting and promoter pull-down assay, we show that collagen type I-activated Discoidin Domain Receptor 2 (DDR2) mediates Angiotensin II-stimulated transcriptional up-regulation of fibronectin expression by Yes-activated Protein in cardiac fibroblasts. Further, siRNA-mediated fibronectin knockdown attenuated Angiotensin II-dependent expression of anti-apoptotic cIAP2 and promoted cell death under oxidative stress. Fibronectin was also found to mediate Angiotensin II-stimulated collagen type I expression. Importantly, an obligate role for fibronectin was observed in Angiotensin II-stimulated expression of its receptor, AT1R, which would link ECM signalling and Angiotensin II signalling in cardiac fibroblasts. Moreover, the regulatory role of DDR2-dependent fibronectin expression in Ang II-stimulated cIAP2, collagen type I and AT1R expression was mediated by Integrin-β1-integrin-linked kinase signalling. The pro-survival role of fibronectin in cardiac fibroblasts and its regulatory role in collagen and AT1R expression, downstream of DDR2, could be critical determinants of cardiac fibroblast-mediated wound healing following myocardial injury. Our findings point to a complex mechanism of regulation of cardiac fibroblast function involving two major extracellular matrix proteins, collagen type I and fibronectin, and their receptors, DDR2 and Integrin-β1.

Nicotine Induces Collagen Type I Expression In Lung: Role Of Fibroblasts And Implications For Tobacco-Related Inflammation

2011 ◽  
Author(s):  
Glenn W. Vicary ◽  
Edilson Torres-Gonzalez ◽  
Tanmay S. Panchabhai ◽  
Jeffrey D. Ritzenthaler ◽  
Jesse Roman
Keyword(s):  
Collagen Type ◽  
Collagen Type I ◽  
Type I

scholarly journals Type I toxin-antitoxin systems contribute to the maintenance of mobile genetic elements in Clostridioides difficile

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Johann Peltier ◽  
Audrey Hamiot ◽  
Julian R. Garneau ◽  
Pierre Boudry ◽  
Anna Maikova ◽  
...  
Keyword(s):  
Ectopic Expression ◽  
Mobile Genetic Elements ◽  
Toxin Gene ◽  
Type I ◽  
Genetic Elements ◽  
Clostridioides Difficile ◽  
Bacterial Chromosomes ◽  
Toxin Protein

AbstractToxin-antitoxin (TA) systems are widespread on mobile genetic elements and in bacterial chromosomes. In type I TA, synthesis of the toxin protein is prevented by the transcription of an antitoxin RNA. The first type I TA were recently identified in the human enteropathogen Clostridioides difficile. Here we report the characterization of five additional type I TA within phiCD630-1 (CD0977.1-RCd11, CD0904.1-RCd13 and CD0956.3-RCd14) and phiCD630-2 (CD2889-RCd12 and CD2907.2-RCd15) prophages of C. difficile strain 630. Toxin genes encode 34 to 47 amino acid peptides and their ectopic expression in C. difficile induces growth arrest that is neutralized by antitoxin RNA co-expression. We show that type I TA located within the phiCD630-1 prophage contribute to its stability and heritability. We have made use of a type I TA toxin gene to generate an efficient mutagenesis tool for this bacterium that allowed investigation of the role of these widespread TA in prophage maintenance.

scholarly journals The “central vein sign” in inflammatory demyelination: The role of fibrillar collagen type I

2019 ◽  
Vol 85 (6) ◽  
pp. 934-942 ◽  
Author(s):  
Martina Absinta ◽  
Govind Nair ◽  
Maria Chiara G. Monaco ◽  
Dragan Maric ◽  
Nathanael J. Lee ◽  
...  
Keyword(s):  
Collagen Type ◽  
Collagen Type I ◽  
Central Vein ◽  
Type I ◽  
Fibrillar Collagen
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