scholarly journals Evaluation of the antifibrotic potency by knocking down SPARC, CCR2 and SMAD3

2018 ◽  
Author(s):  
Weifeng Ding ◽  
Weilin Pu ◽  
Shuai Jiang ◽  
Yanyun Ma ◽  
Qingmei Liu ◽  
...  
Keyword(s):  
Inflammatory Cells ◽  
Cell Types ◽  
Biological Pathways ◽  
Triple Combination ◽  
Aberrant Expression ◽  
Mouse Tissues ◽  
Peptide Nanoparticles ◽  
Fibrotic Disorders ◽  
Combination Of Sirnas ◽  
Different Cell Types

AbstractThe genes of SPARC, CCR2, and SMAD3 are implicated in orchestrating inflammation and fibrosis in scleroderma and other fibrotic disorders. Aim of the studies was to examine synergistic effect of inhibition of these genes in treating fibrosis. The peptide nanoparticles were used to deliver the siRNAs in bleomycin-induced fibrotic mice. Triple combination of siRNAs targeting on Sparc, Ccr2 and Smad3 achieved favorable anti-inflammatory and anti-fibrotic effects. Inhibition of inflammation was evidenced by reduced inflammatory cells and proinflammatory cytokines in the BALF and/or the tissues. Activation of fibroblasts was suppressed in mouse tissues in which α-Sma and collagens were significantly reduced. Aberrant expression of the genes in fibroblasts, monocytes/macrophage, endothelial and epithelial cells were reinstalled after the treatment. In addition, transcriptome profiles indicated that some bleomycin-induced alterations of multiple biological pathways were recovered to varying degrees by the treatment. The results indicated that the triple combination of siRNAs systemically reinstated multiple biopathways, probably through controlling on different cell types including fibroblasts, monocytes/macrophages, endothelial cells and others. The multi-target-combined therapeutic approach examined herein may represent a novel and effective therapy for fibrosis.

Implications of microRNAs in the pathogenesis of atherosclerosis and prospects for therapy

2021 ◽  
Vol 22 ◽  
Author(s):  
Armita Mahdavi Gorabi ◽  
Mohsen Ghanbari ◽  
Thozhukat Sathyapalan ◽  
Tannaz Jamialahmadi ◽  
Amirhossein Sahebkar
Keyword(s):  
Immune Cell ◽  
Cholesterol Metabolism ◽  
Current Knowledge ◽  
Inflammatory Cells ◽  
Cell Types ◽  
Fine Tuning ◽  
Lipid Uptake ◽  
Atherosclerosis Development ◽  
Signaling Receptors ◽  
Different Cell Types

MicroRNAs (miRNAs) are non-coding RNAs containing around 22 nucleotides, which are expressed in vertebrates and plants. They act as posttranscriptional gene expression regulators, fine-tuning various biological processes in different cell types. There is emerging evidence on their role in different stages of atherosclerosis. In addition to regulating the inflammatory cells involved in atherosclerosis, miRNAs play fundamental roles in the pathophysiology of atherosclerosis such as endothelial cell (EC) dysfunction, the aberrant function of the vascular smooth muscle cell (VSMC) and cholesterol metabolism. Moreover, miRNAs participate in several pathogenic pathways of atherosclerotic plaque development, including their effects on immune cell signaling receptors and lipid uptake. In this study, we review our current knowledge of the regulatory role of miRNAs in various pathogenic pathways underlying atherosclerosis development and also outline potential clinical applications of miRNAs in atherosclerosis.

scholarly journals Interleukin-33 and Inflammatory Bowel Diseases: Lessons from Human Studies

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Tiago Nunes ◽  
Claudio Bernardazzi ◽  
Heitor S. de Souza
Keyword(s):  
Inflammatory Bowel Diseases ◽  
Intestinal Inflammation ◽  
Inflammatory Cells ◽  
Cell Types ◽  
Parasitic Infections ◽  
Predominant Role ◽  
Interleukin 33 ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
Different Cell Types

Interleukin- (IL-) 33 is a widely expressed cytokine present in different cell types, such as epithelial, mesenchymal, and inflammatory cells, supporting a predominant role in innate immunity. IL-33 can function as a proinflammatory cytokine inducing Th2 type of immune response being involved with the defense against parasitic infections of the gastrointestinal tract. In addition, it has been proposed that IL-33 can act as a signaling molecule alerting the immune system of danger or tissue damage. Recently, in the intestinal mucosa, overexpression of IL-33 has been reported in samples from patients with inflammatory bowel diseases (IBD). This review highlights the available data regarding IL-33 in human IBD and discusses emerging roles for IL-33 as a key modulator of intestinal inflammation.

The Cytokine Network: Their Role in Physiopathology and Therapeutic Implications

1992 ◽  
Vol 5 (2) ◽  
pp. 67-76 ◽  
Author(s):  
G. Ricevuti ◽  
A. Mazzone ◽  
D. Pasotti ◽  
A. Notario
Keyword(s):  
Inflammatory Cells ◽  
Cell Types ◽  
Clinical Implications ◽  
Rapid Progress ◽  
Cytokine Network ◽  
Therapeutic Implications ◽  
Complex Interactions ◽  
Haematopoietic Cells ◽  
Human Disorders ◽  
Different Cell Types

Lymphocytes, accessory-endothelial-and inflammatory-cells produce a variety of soluble factors termed cytokines. These are regulatory molecules which appear after the immune response at all stages of lymphocyte development. They also have important regulatory influences on other haematopoietic cells. Rapid progress is being made through the use of gene cloned cytokines in understanding the complex interactions of these factors with many different cell types. New factors have been added to the cytokine network, and new functions reported for existing cytokines. The clinical implications in disease and the application of cytokines or their inhibitors in human disorders, cancer, infection and autoimmunity, has met with some success and many trials are currently in progress which should lead to more successful therapeutic strategies.

scholarly journals Tumor angiogenesis and progression are enhanced by Sema4D produced by tumor-associated macrophages

2008 ◽  
Vol 205 (7) ◽  
pp. 1673-1685 ◽  
Author(s):  
Jose Rafael Sierra ◽  
Simona Corso ◽  
Luisa Caione ◽  
Virna Cepero ◽  
Paolo Conrotto ◽  
...  
Keyword(s):  
Tumor Angiogenesis ◽  
Tumor Stroma ◽  
Inflammatory Cells ◽  
Cell Types ◽  
Tumor Associated Macrophages ◽  
Semaphorin 4D ◽  
Vessel Maturation ◽  
Different Cell Types ◽  
Novel Therapeutic

Increased evidence suggests that cancer-associated inflammation supports tumor growth and progression. We have previously shown that semaphorin 4D (Sema4D), a ligand produced by different cell types, is a proangiogenic molecule that acts by binding to its receptor, plexin B1, expressed on endothelial cells (Conrotto, P., D. Valdembri, S. Corso, G. Serini, L. Tamagnone, P.M. Comoglio, F. Bussolino, and S. Giordano. 2005. Blood. 105:4321–4329). The present work highlights the role of Sema4D produced by the tumor microenvironment on neoplastic angiogenesis. We show that in an environment lacking Sema4D, the ability of cancer cells to generate tumor masses and metastases is severely impaired. This condition can be explained by a defective vascularization inside the tumor. We demonstrate that tumor-associated macrophages (TAMs) are the main cells producing Sema4D within the tumor stroma and that their ability to produce Sema4D is critical for tumor angiogenesis and vessel maturation. This study helps to explain the protumoral role of inflammatory cells of the tumor stroma and leads to the identification of an angiogenic molecule that might be a novel therapeutic target.

scholarly journals Mouse lipidomics reveals inherent flexibility of a mammalian lipidome

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Michał A. Surma ◽  
Mathias J. Gerl ◽  
Ronny Herzog ◽  
Jussi Helppi ◽  
Kai Simons ◽  
...  
Keyword(s):  
Quantitative Assessment ◽  
Pharmaceutical Research ◽  
Cell Types ◽  
Model Organisms ◽  
Murine Models ◽  
Systematic Analysis ◽  
Bodily Fluids ◽  
Mouse Tissues ◽  
Organ Specific ◽  
Different Cell Types

AbstractLipidomics has become an indispensable method for the quantitative assessment of lipid metabolism in basic, clinical, and pharmaceutical research. It allows for the generation of information-dense datasets in a large variety of experimental setups and model organisms. Previous studies, mostly conducted in mice (Mus musculus), have shown a remarkable specificity of the lipid compositions of different cell types, tissues, and organs. However, a systematic analysis of the overall variation of the mouse lipidome is lacking. To fill this gap, in the present study, the effect of diet, sex, and genotype on the lipidomes of mouse tissues, organs, and bodily fluids has been investigated. Baseline quantitative lipidomes consisting of 796 individual lipid molecules belonging to 24 lipid classes are provided for 10 different sample types. Furthermore, the susceptibility of lipidomes to the tested parameters is assessed, providing insights into the organ-specific lipidomic plasticity and flexibility. This dataset provides a valuable resource for basic and pharmaceutical researchers working with murine models and complements existing proteomic and transcriptomic datasets. It will inform experimental design and facilitate interpretation of lipidomic datasets.

scholarly journals MicroRNAs: Recent insights towards their role in male infertility and reproductive cancers

2019 ◽  
Vol 19 (1) ◽  
pp. 31-42 ◽  
Author(s):  
Muhammad Babar Khawar ◽  
Rabia Mehmood ◽  
Nabila Roohi
Keyword(s):  
Male Infertility ◽  
Reproductive System ◽  
Molecular Mechanisms ◽  
Cell Types ◽  
Regulatory Mechanisms ◽  
Aberrant Expression ◽  
Protein Coding ◽  
Reproductive Cancers ◽  
Post Transcriptional Regulation ◽  
Different Cell Types

Spermatogenesis is a tightly controlled, multi-step process in which mature spermatozoa are produced. Disruption of regulatory mechanisms in spermatogenesis can lead to male infertility, various diseases of male reproductive system, or even cancer. The spermatogenic impairment in infertile men can be associated with different etiologies, and the exact molecular mechanisms are yet to be determined. MicroRNAs (miRNAs) are a type of non-protein coding RNAs, about 22 nucleotides long, with an essential role in post-transcriptional regulation. miRNAs have been recognized as important regulators of various biological processes, including spermatogenesis. The aim of this review is to summarize the recent literature on the role of miRNAs in spermatogenesis, male infertility and reproductive cancers, and to evaluate their potential in diagnosis, prognosis and therapy of disease. Experimental evidence shows that aberrant expression of miRNAs affects spermatogenesis at multiple stages and in different cell types, most often resulting in infertility. In more severe cases, dysregulation of miRNAs leads to cancer. miRNAs have enormous potential to be used as diagnostic and prognostic markers as well as therapeutic targets in male infertility and reproductive system diseases. However, to exploit this potential fully, we need a better understanding of miRNA-mediated regulation of spermatogenesis, including the characterization of yet unidentified miRNAs and related regulatory mechanisms.

Inhibition of SFRP1 Reduces Severity of Periodontitis

2007 ◽  
Vol 86 (9) ◽  
pp. 873-877 ◽  
Author(s):  
C.H. Li ◽  
S. Amar
Keyword(s):  
Inflammatory Cell ◽  
Inflammatory Responses ◽  
Inflammatory Cells ◽  
Cell Types ◽  
Inflammatory Cell Infiltrate ◽  
Periodontal Tissues ◽  
Periodontal Breakdown ◽  
Common Infectious Disease ◽  
Apoptosis Assay ◽  
Different Cell Types

Porphyromonas gingivalis ( P. gingivalis) is implicated as a major pathogen in periodontitis, a common infectious disease characterized by the inflammation and destruction of periodontal tissues. Secreted frizzled-related protein 1 (SFRP1) modulates apoptosis in different cell types. To characterize the roles of SFRP1 in periodontitis, we used a P. gingivalis-induced murine periodontitis model. Inflammatory responses were measured by morphometric and histomorphometric analysis, apoptosis assay, and immunohistochemistry. We found that P. gingivalis-infected mouse periodontal tissues expressed significantly more SFRP1 compared with those of control mice. Also, in P. gingivalis-infected animals, more apoptosis of inflammatory cells, fibroblasts, and bone-lining cells was observed compared with controls. Antibody experiments aimed at inhibiting SFRP1 expression in periodontitis resulted in a reduction of periodontal breakdown, inflammatory cell infiltrate, osteoclastogenesis, and apoptosis of inflammatory cells and fibroblasts. The results of our studies suggest that SFRP1 may be involved in the development of periodontitis, since inhibiting SFRP1 resulted in reduced periodontal breakdown.

scholarly journals Unveiling the ups and downs of miR-205 in physiology and cancer: transcriptional and post-transcriptional mechanisms

2020 ◽  
Vol 11 (11) ◽  
Author(s):  
Elena Ferrari ◽  
Paolo Gandellini
Keyword(s):  
Epithelial Cell ◽  
Target Genes ◽  
Cell Function ◽  
Cell Types ◽  
Future Application ◽  
Transcriptional Level ◽  
Aberrant Expression ◽  
Specific Tumor ◽  
And Function ◽  
Different Cell Types

Abstract miR-205 plays important roles in the physiology of epithelia by regulating a variety of pathways that govern differentiation and morphogenesis. Its aberrant expression is frequently found in human cancers, where it was reported to act either as tumor-suppressor or oncogene depending on the specific tumor context and target genes. miR-205 expression and function in different cell types or processes are the result of the complex balance among transcription, processing and stability of the microRNA. In this review, we summarize the principal mechanisms that regulate miR-205 expression at the transcriptional and post-transcriptional level, with particular focus on the transcriptional relationship with its host gene. Elucidating the mechanisms and factors regulating miR-205 expression in different biological contexts represents a fundamental step for a better understanding of the contribution of such pivotal microRNA to epithelial cell function in physiology and disease, and for the development of modulation strategies for future application in cancer therapy.

scholarly journals Joint reconstruction of cis-regulatory interaction networks across multiple tissues using single-cell chromatin accessibility data

2020 ◽  
Author(s):  
Kangning Dong ◽  
Shihua Zhang
Keyword(s):  
Single Cell ◽  
Regulatory Networks ◽  
Cell Types ◽  
Chromatin Accessibility ◽  
Computational Method ◽  
Regulatory Mechanisms ◽  
Regulatory Interaction ◽  
Regulatory Interactions ◽  
Mouse Tissues ◽  
Different Cell Types

Abstract The rapid accumulation of single-cell chromatin accessibility data offers a unique opportunity to investigate common and specific regulatory mechanisms across different cell types. However, existing methods for cis-regulatory network reconstruction using single-cell chromatin accessibility data were only designed for cells belonging to one cell type, and resulting networks may be incomparable directly due to diverse cell numbers of different cell types. Here, we adopt a computational method to jointly reconstruct cis-regulatory interaction maps (JRIM) of multiple cell populations based on patterns of co-accessibility in single-cell data. We applied JRIM to explore common and specific regulatory interactions across multiple tissues from single-cell ATAC-seq dataset containing ~80 000 cells across 13 mouse tissues. Reconstructed common interactions among 13 tissues indeed relate to basic biological functions, and individual cis-regulatory networks show strong tissue specificity and functional relevance. More importantly, tissue-specific regulatory interactions are mediated by coordination of histone modifications and tissue-related TFs, and many of them may reveal novel regulatory mechanisms.

scholarly journals Exosomal MiRNAs in Pediatric Cancers

2019 ◽  
Vol 20 (18) ◽  
pp. 4600 ◽  
Author(s):  
Angela Galardi ◽  
Marta Colletti ◽  
Virginia Di Paolo ◽  
Patrizia Vitullo ◽  
Loretta Antonetti ◽  
...  
Keyword(s):  
Biological Fluids ◽  
Regulation Of Gene Expression ◽  
Cell Types ◽  
Aberrant Expression ◽  
Pediatric Cancers ◽  
Exosomal Mirnas ◽  
Rhabdoid Tumors ◽  
Almost All ◽  
Invasive Techniques ◽  
Different Cell Types

MicroRNAs (miRNAs) have generated great attention in oncology as they play a fundamental role in the regulation of gene expression and their aberrant expression is present in almost all types of tumors including pediatric ones. The discovery that miRNAs can be transported by exosomes, which are vesicles of 40–120 nm involved in cellular communication, that are produced by different cell types, and that are present in different biological fluids, has opened the possibility of using exosomal miRNAs as biomarkers. The possibility to diagnose and monitor the progression and response to drugs through molecules that can be easily isolated from biological fluids represents a particularly important aspect in the pediatric context where invasive techniques are often used. In recent years, the idea of liquid biopsy as well as studies on the possible role of exosomal miRNAs as biomarkers have developed greatly. In this review, we report an overview of all the evidences acquired in recent years on the identification of exosomal microRNAs with biomarker potential in pediatric cancers. We discuss the following herein: neuroblastoma, hepatoblastoma, sarcomas (osteosarcoma, Ewing’s sarcoma and rhabdoid tumors, and non-rhabdomyosarcoma soft tissue sarcoma), brain tumors, lymphomas, and leukemias.

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