scholarly journals Cytokine-Mediated Alterations of Human Cardiac Fibroblast’s Secretome

2021 ◽  
Vol 22 (22) ◽  
pp. 12262
Author(s):  
Hanna Bräuninger ◽  
Tilo Thottakara ◽  
Jacob Schön ◽  
Svenja Voss ◽  
Vishnu Dhople ◽  
...  
Keyword(s):  
Cardiac Fibroblasts ◽  
Transcriptome Profiling ◽  
Secreted Proteins ◽  
Cytokine Gene Expression ◽  
Expression Of Genes ◽  
Collagen Secretion ◽  
Tnf Α ◽  
Inflammatory Processes ◽  
Extracellular Stimuli ◽  
Human Cardiac Fibroblasts

Fibroblasts contribute to approximately 20% of the non-cardiomyocytic cells in the heart. They play important roles in the myocardial adaption to stretch, inflammation, and other pathophysiological conditions. Fibroblasts are a major source of extracellular matrix (ECM) proteins whose production is regulated by cytokines, such as TNF-α or TGF-β. The resulting myocardial fibrosis is a hallmark of pathological remodeling in dilated cardiomyopathy (DCM). Therefore, in the present study, the secretome and corresponding transcriptome of human cardiac fibroblasts from patients with DCM was investigated under normal conditions and after TNF-α or TGF-β stimulation. Secreted proteins were quantified via mass spectrometry and expression of genes coding for secreted proteins was analyzed via Affymetrix Transcriptome Profiling. Thus, we provide comprehensive proteome and transcriptome data on the human cardiac fibroblast’s secretome. In the secretome of quiescent fibroblasts, 58% of the protein amount belonged to the ECM fraction. Interestingly, cytokines were responsible for 5% of the total protein amount in the secretome and up to 10% in the corresponding transcriptome. Furthermore, cytokine gene expression and secretion were upregulated upon TNF-α stimulation, while collagen secretion levels were elevated after TGF-β treatment. These results suggest that myocardial fibroblasts contribute to pro-fibrotic and to inflammatory processes in response to extracellular stimuli.

AB23A Reduces TGF-β1-Induced Human Cardiac Fibroblasts (HCF) Proliferation and Collagen Secretion via MER/ERK1/2/CREB Pathway

2020 ◽  
Vol 10 (6) ◽  
pp. 798-803
Author(s):  
Dinghui Hu ◽  
Yanhu Wu ◽  
Jin Du ◽  
Hang Li ◽  
Zuntao Liu
Keyword(s):  
Western Blot ◽  
Signaling Pathway ◽  
Myocardial Fibrosis ◽  
Cardiac Fibroblasts ◽  
Heart Diseases ◽  
Protein Levels ◽  
Collagen Secretion ◽  
Assay Result ◽  
Human Cardiac Fibroblasts ◽  
Creb Pathway

Background and Objectives: Myocardial fibrosis is associated with many forms of heart diseases which is characterized by the accumulation of activated cardiac fibroblasts (CFBs) and excess deposition of extracellular matrix (ECM). Natural compounds such as Alisol B 23-acetate has been proved to maintain the activation of ERK1/2, but whether it can affect cardiac fibroblasts by MER/ERK1/2/CREB signaling pathway is still unknown. Methods: The cell was identified with α-SMA protein level detected by immunofluorescence staining method. The cell proliferation was examined by CCK8 assay. Col I and Col III protein levels were examined by western blot and sirius red staining to detect the ECM level. Furthermore, p-MERK, MERK, P-ERK, ERK and CREB were examined by western blot to verify whether Alisol could activate the MERK/ERK1/2/CREB pathway in myocardial fibrosis. Results: CCK8 assay result indicated that Alisol reduced the cell viability of CFBs induced by TGF-β1. In addition, Alisol significantly decreased the ECM deposition of CFBs. Furthermore, Alisol could activate MERK/ERK1/2/CREB signaling pathway. Conclusion: These results verified that Alisol inhibited myocardial fibrosis via MERK/ERK1/2/CREB pathway.

scholarly journals NADPH Oxidase/ROS-Dependent VCAM-1 Induction on TNF-α-Challenged Human Cardiac Fibroblasts Enhances Monocyte Adhesion

2016 ◽  
Vol 6 ◽  
Author(s):  
Chih-Chung Lin ◽  
Chien-Chung Yang ◽  
Chen-Yu Wang ◽  
Hui-Ching Tseng ◽  
Chih-Shuo Pan ◽  
...  
Keyword(s):  
Nadph Oxidase ◽  
Cardiac Fibroblasts ◽  
Monocyte Adhesion ◽  
Tnf Α ◽  
Human Cardiac Fibroblasts

scholarly journals Upregulation of COX-2 and PGE2 Induced by TNF-α Mediated Through TNFR1/MitoROS/PKCα/P38 MAPK, JNK1/2/FoxO1 Cascade in Human Cardiac Fibroblasts

2021 ◽  
Vol Volume 14 ◽  
pp. 2807-2824
Author(s):  
Chuen-Mao Yang ◽  
Chien-Chung Yang ◽  
Li-Der Hsiao ◽  
Chia-Ying Yu ◽  
Hui-Ching Tseng ◽  
...  
Keyword(s):  
P38 Mapk ◽  
Cardiac Fibroblasts ◽  
Tnf Α ◽  
Cox 2 ◽  
Human Cardiac Fibroblasts

Role of inflammation in the development of colorectal cancer

2020 ◽  
Vol 20 ◽  
Author(s):  
Sridhar Muthusami ◽  
R. Ileng Kumaran ◽  
Kokelavani Nampalli Babu ◽  
Sneha Krishnamoorthy ◽  
Akash Guruswamy ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Chronic Inflammation ◽  
Interleukin 1 ◽  
Cell Types ◽  
Model Systems ◽  
Cytokine Gene Expression ◽  
Necrosis Factor Alpha ◽  
Tnf Α ◽  
Proinflammatory Molecules

: Chronic inflammation can lead to the development of many diseases including cancer. Inflammatory bowel disease (IBD) that includes both ulcerative colitis (UC) and Crohn's disease (CD) are risk factors for the development of colorectal cancer (CRC). Many cytokines produced primarily by the gut immune cells either during or in response to localized inflammation in the colon and rectum are known to stimulate the complex interactions between the different cell types in the gut environment resulting in acute inflammation. Subsequently, chronic inflammation together with genetic and epigenetic changes has been shown to lead to the development and progression of CRC. Various cell types present in the colon such as enterocytes, Paneth cells, goblet cells and macrophages express receptors for inflammatory cytokines and respond to tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), IL-6 and other cytokines. Among the several cytokines produced, TNF-α and IL-1β are the key proinflammatory molecules that play critical roles in the development of CRC. The current review is intended to consolidate the published findings to focus on the role of proinflammatory cytokines, namely TNF-α and IL-1β, on inflammation (and the altered immune response) in the gut, to better understand the development of CRC in IBD, using various experimental model systems, preclinical and clinical studies. Moreover, this review also highlights the current therapeutic strategies available (monotherapy and combination therapy), to alleviate the symptoms or treat inflammationassociated CRC by using monoclonal antibodies or aptamers to block proinflammatory molecules, inhibitors of tyrosine kinases in inflammatory signaling cascade, competitive inhibitors of proinflammatory molecules, and the nucleic acid drugs like small activating RNAs (saRNAs) or microRNA (miRNA) mimics to activate tumor suppressor or repress oncogene/proinflammatory cytokine gene expression.

scholarly journals Transcriptomic Analysis of Short-Term Salt-Stress Response in Mega Hybrid Rice Seedlings

Agronomy ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 1328
Author(s):  
Noushin Jahan ◽  
Yang Lv ◽  
Mengqiu Song ◽  
Yu Zhang ◽  
Liangguang Shang ◽  
...  
Keyword(s):  
Salt Stress ◽  
Molecular Mechanisms ◽  
Oryza Sativa L ◽  
Transcriptome Profiling ◽  
Bhlh Transcription Factor ◽  
F1 Hybrid ◽  
Salt Stress Response ◽  
Productivity Losses ◽  
Expression Of Genes ◽  
Trait Locus

Salinity is a major abiotic stressor that leads to productivity losses in rice (Oryza sativa L.). In this study, transcriptome profiling and heterosis-related genes were analyzed by ribonucleic acid sequencing (RNA-Seq) in seedlings of a mega rice hybrid, Liang-You-Pei-Jiu (LYP9), and its two parents 93–11 and Pei-ai64s (PA64s), under control and two different salinity levels, where we found 8292, 8037, and 631 salt-induced differentially expressed genes (DEGs), respectively. Heterosis-related DEGs were obtained higher after 14 days of salt treatment than after 7 days. There were 631 and 4237 salt-induced DEGs related to heterosis under 7-day and 14-day salt stresses, respectively. Gene functional classification showed the expression of genes involved in photosynthesis activity after 7-day stress treatment, and in metabolic and catabolic activity after 14 days. In addition, we correlated the concurrence of an expression of DEGs for the bHLH transcription factor and a shoot length/salinity-related quantitative trait locus qSL7 that we fine-mapped previously, providing a confirmed case of heterosis-related genes. This experiment reveals the transcriptomic divergence of the rice F1 hybrid and its parental lines under control and salt stress state, and enlightens about the significant molecular mechanisms developed over time in response to salt stress.

scholarly journals Menstrual Blood-Derived Endometrial Stem Cells’ Impact for the Treatment Perspective of Female Infertility

2021 ◽  
Vol 22 (13) ◽  
pp. 6774
Author(s):  
Giedrė Skliutė ◽  
Raminta Baušytė ◽  
Veronika Borutinskaitė ◽  
Giedrė Valiulienė ◽  
Algirdas Kaupinis ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell Differentiation ◽  
Embryonic Cell ◽  
Menstrual Blood ◽  
Endometrial Stem Cells ◽  
Expression Of Genes ◽  
Menstrual Blood Stem Cells ◽  
Marrow Mesenchymal Stem Cells ◽  
Blood Stem Cells ◽  
Inflammatory Processes

When looking for the causes and treatments of infertility, much attention is paid to one of the reproductive tissues—the endometrium. Therefore, endometrial stem cells are an attractive target for infertility studies in women of unexplained origin. Menstrual blood stem cells (MenSCs) are morphologically and functionally similar to cells derived directly from the endometrium; with dual expression of mesenchymal and embryonic cell markers, they proliferate and regenerate better than bone marrow mesenchymal stem cells. In addition, menstrual blood stem cells are extracted in a non-invasive and painless manner. In our study, we analyzed the characteristics and the potential for decidualization of menstrual blood stem cells isolated from healthy volunteers and women diagnosed with infertility. We demonstrated that MenSCs express CD44, CD166, CD16, CD15, BMSC, CD56, CD13 and HLA-ABC surface markers, have proliferative properties, and after induction of menstrual stem cell differentiation into epithelial direction, expression of genes related to decidualization (PRL, ESR, IGFBP and FOXO1) and angiogenesis (HIF1, VEGFR2 and VEGFR3) increased. Additionally, the p53, p21, H3K27me3 and HyperAcH4 proteins’ expression increased during MenSCs decidualization, they secrete proteins that are involved in the regulation of the actin cytoskeleton, estrogen and relaxin signaling pathways and the management of inflammatory processes. Our findings reveal the potential use of MenSCs for the treatment of reproductive disorders.

scholarly journals A protocol for transdifferentiation of human cardiac fibroblasts into endothelial cells via activation of innate immunity

2021 ◽  
Vol 2 (2) ◽  
pp. 100556
Author(s):  
Chun Liu ◽  
Pedro Medina ◽  
Dilip Thomas ◽  
Ian Y. Chen ◽  
Karim Sallam ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Endothelial Cells ◽  
Cardiac Fibroblasts ◽  
Human Cardiac Fibroblasts

Effects of methylglyoxal on human cardiac fibroblast: roles of transient receptor potential ankyrin 1 (TRPA1) channels

2014 ◽  
Vol 307 (9) ◽  
pp. H1339-H1352 ◽  
Author(s):  
Gaku Oguri ◽  
Toshiaki Nakajima ◽  
Yumiko Yamamoto ◽  
Nami Takano ◽  
Tomofumi Tanaka ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Diabetic Cardiomyopathy ◽  
Cell Cycle Progression ◽  
Transient Receptor Potential ◽  
Cardiac Fibroblasts ◽  
Receptor Potential ◽  
Rt Pcr ◽  
Cycle Progression ◽  
Transient Receptor ◽  
Human Cardiac Fibroblasts

Cardiac fibroblasts contribute to the pathogenesis of cardiac remodeling. Methylglyoxal (MG) is an endogenous carbonyl compound produced under hyperglycemic conditions, which may play a role in the development of pathophysiological conditions including diabetic cardiomyopathy. However, the mechanism by which this occurs and the molecular targets of MG are unclear. We investigated the effects of MG on Ca2+ signals, its underlying mechanism, and cell cycle progression/cell differentiation in human cardiac fibroblasts. The conventional and quantitative real-time RT-PCR, Western blot, immunocytochemical analysis, and intracellular Ca2+ concentration [Ca2+]i measurement were applied. Cell cycle progression was assessed using the fluorescence activated cell sorting. MG induced Ca2+ entry concentration dependently. Ruthenium red (RR), a general cation channel blocker, and HC030031 , a selective transient receptor potential ankyrin 1 (TRPA1) antagonist, inhibited MG-induced Ca2+ entry. Treatment with aminoguanidine, a MG scavenger, also inhibited it. Allyl isothiocyanate, a selective TRPA1 agonist, increased Ca2+ entry. The use of small interfering RNA to knock down TRPA1 reduced the MG-induced Ca2+ entry as well as TRPA1 mRNA expression. The quantitative real-time RT-PCR analysis showed the prominent existence of TRPA1 mRNA. Expression of TRPA1 protein was confirmed by Western blotting and immunocytochemical analyses. MG promoted cell cycle progression from G0/G1 to S/G2/M, which was suppressed by HC030031 or RR. MG also enhanced α-smooth muscle actin expression. The present results suggest that methylglyoxal activates TRPA1 and promotes cell cycle progression and differentiation in human cardiac fibroblasts. MG might participate the development of pathophysiological conditions including diabetic cardiomyopathy via activation of TRPA1.

Abstract 367: Lysyl Oxidase Expression by Cardiac Fibroblasts is Regulated by Integrin-mediated Signaling

2015 ◽  
Vol 117 (suppl_1) ◽  
Author(s):  
Albert Gao ◽  
Lauren D Black
Keyword(s):  
Gene Expression ◽  
Cardiac Fibrosis ◽  
Lysyl Oxidase ◽  
Cardiac Fibroblasts ◽  
Therapeutic Strategies ◽  
Expression Of Genes ◽  
Adverse Remodeling ◽  
Novel Therapeutic Strategies ◽  
Free Media ◽  
Tgf Β1

Cardiac fibrosis following myocardial infarction (MI) leads to reduced cardiac function, and contributes to heart failure and mortality. Recent studies shown the extent of adverse remodeling may be mitigated by therapeutic strategies which regulate cardiac fibroblast mediated-remodeling. Since cross-linking by lysyl oxidase (LOX) increases following MI and alters the mechanical properties of the infarct, it is critical to characterize how its expression is regulated by CFs post-MI. While LOX expression is attributable to TGF-β1 signaling, we hypothesize that changes in the stiffness and composition of the ECM can also alter LOX expression via integrin-mediated signaling. To investigate this, we isolated CFs from healthy left ventricle (LV) and infarcted cardiac fibroblasts (ICFs) from 1 week post-MI LV and cultured them on tissue culture plastic (TCP) and collagen I-coated plates (COL) in serum-free media for 48 hours to assess the expression of genes associated with LOX signaling, fibrosis, and myofibroblast activation. Our results show an upregulation of LOX gene expression in both CFs and ICFs when cultured on COL and this is further emphasized with the presence of TGF-β1 (Fig. 1A). Gene expression of col1α1, integrin β1 subunit and αSMA (Fig. 1B-D) also exhibit similar upregulation. Ongoing studies will investigate how altered substrate stiffness and composition affect gene expression of LOX and other genes associated with fibrosis. By understanding the effect of the physical microenvironment on the expression of fibrotic genes including LOX, we aim to develop novel therapeutic strategies to attenuate cardiac fibrosis and thus improve cardiac recovery following MI.

Alterations in T-Cell Transcription Factors and Cytokine Gene Expression in Late-Onset Alzheimer’s Disease

2021 ◽  
pp. 1-21
Author(s):  
Masoud Neshan ◽  
Seyed Kazem Malakouti ◽  
Leila Kamalzadeh ◽  
Mina Makvand ◽  
Arezoo Campbell ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Transcription Factors ◽  
T Cell ◽  
Late Onset ◽  
Cytokine Gene Expression ◽  
Mrna Levels ◽  
Tnf Α ◽  
Significant Difference ◽  
Ifn Γ

Background: Late-onset Alzheimer’s disease (LOAD) is associated with many environmental and genetic factors. The effect of systemic inflammation on the pathogenesis of neurodegenerative diseases such as AD has been strongly suggested. T helper cells (Th) are one of the important components of the immune system and can easily infiltrate the brain in pathological conditions. The development of each Th-subset depends on the production of unique cytokines and their main regulator. Objective: This study aimed to compare the mRNA levels of Th-related genes derived from peripheral blood mononuclear cells of LOAD patients with control. Also, the identification of the most important Th1/Th2 genes and downstream pathways that may be involved in the pathogenesis of AD was followed by computational approaches. Methods: This study invloved 30 patients with LOAD and 30 non-demented controls. The relative expression of T-cell cytokines (IFN-γ, TNF-α, IL-4, and IL-5) and transcription factors (T-bet and GATA-3) were assessed using real-time PCR. Additionally, protein-protein interaction (PPI) was investigated by gene network construction. Results: A significant decrease at T-bet, IFN-γ, TNF-α, and GATA-3 mRNA levels was detected in the LOAD group, compared to the controls. However, there was no significant difference in IL-4 or IL-5 mRNA levels. Network analysis revealed a list of the highly connected protein (hubs) related to mitogen-activated protein kinase (MAPK) signaling and Th17 cell differentiation pathways. Conclusion: The findings point to a molecular dysregulation in Th-related genes, which can promising in the early diagnosis or targeted interventions of AD. Furthermore, the PPI analysis showed that upstream off-target stimulation may involve MAPK cascade activation and Th17 axis induction.

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