scholarly journals Insights into Macrophage/Monocyte-Endothelial Cell Crosstalk in the Liver: A Role for Trem-2

2021 ◽  
Vol 10 (6) ◽  
pp. 1248
Author(s):  
Inês Coelho ◽  
Nádia Duarte ◽  
Maria Paula Macedo ◽  
Carlos Penha-Gonçalves
Keyword(s):  
Endothelial Cells ◽  
Tissue Regeneration ◽  
Current Knowledge ◽  
Cell Communication ◽  
Tissue Homeostasis ◽  
Liver Pathology ◽  
Liver Sinusoidal Endothelial Cells ◽  
Cell Compartments ◽  
Cell Crosstalk

Liver disease accounts for millions of deaths worldwide annually being a major cause of global morbidity. Hepatotoxic insults elicit a multilayered response involving tissue damage, inflammation, scar formation, and tissue regeneration. Liver cell populations act coordinately to maintain tissue homeostasis and providing a barrier to external aggressors. However, upon hepatic damage, this tight regulation is disrupted, leading to liver pathology which spans from simple steatosis to cirrhosis. Inflammation is a hallmark of liver pathology, where macrophages and endothelial cells are pivotal players in promoting and sustaining disease progression. Understanding the drivers and mediators of these interactions will provide valuable information on what may contribute to liver resilience against disease. Here, we summarize the current knowledge on the role of macrophages and liver sinusoidal endothelial cells (LSEC) in homeostasis and liver pathology. Moreover, we discuss the expanding body of evidence on cell-to-cell communication between these two cell compartments and present triggering receptor expressed on myeloid cells-2 (Trem-2) as a plausible mediator of this cellular interlink. This review consolidates relevant knowledge that might be useful to guide the pursue of successful therapeutic targets and pharmacological strategies for controlling liver pathogenesis.

scholarly journals Emerging Roles of Liver Sinusoidal Endothelial Cells in Nonalcoholic Steatohepatitis

Biology ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 395
Author(s):  
Kunimaro Furuta ◽  
Qianqian Guo ◽  
Petra Hirsova ◽  
Samar H. Ibrahim
Keyword(s):  
Endothelial Cells ◽  
Adhesion Molecules ◽  
Nonalcoholic Steatohepatitis ◽  
Current Knowledge ◽  
Critical Role ◽  
Public Health Problem ◽  
Liver Sinusoidal Endothelial Cells ◽  
Sinusoidal Endothelial Cells ◽  
And Function

Nonalcoholic steatohepatitis (NASH) has become a growing public health problem worldwide, yet its pathophysiology remains unclear. Liver sinusoidal endothelial cells (LSEC) have unique morphology and function, and play a critical role in liver homeostasis. Emerging literature implicates LSEC in many pathological processes in the liver, including metabolic dysregulation, inflammation, angiogenesis, and carcinogenesis. In this review, we highlight the current knowledge of the role of LSEC in each of the progressive phases of NASH pathophysiology (steatosis, inflammation, fibrosis, and the development of hepatocellular carcinoma). We discuss processes that have important roles in NASH progression including the detrimental transformation of LSEC called “capillarization”, production of inflammatory and profibrogenic mediators by LSEC as well as LSEC-mediated angiogenesis. The current review has a special emphasis on LSEC adhesion molecules, and their key role in the inflammatory response in NASH. Moreover, we discuss the pathogenic role of extracellular vesicles and their bioactive cargos in liver intercellular communication, inflammation, and fibrosis. Finally, we highlight LSEC-adhesion molecules and derived bioactive product as potential therapeutic targets for human NASH.

Neurotoxic and Neuroprotective Role of Exosomes in Parkinson’s Disease

2020 ◽  
Vol 25 (42) ◽  
pp. 4510-4522 ◽  
Author(s):  
Biancamaria Longoni ◽  
Irene Fasciani ◽  
Shivakumar Kolachalam ◽  
Ilaria Pietrantoni ◽  
Francesco Marampon ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Potential Role ◽  
Current Knowledge ◽  
Biological Fluids ◽  
Cell Communication ◽  
Target Cells ◽  
Cellular Debris ◽  
The Brain

: Exosomes are extracellular vesicles produced by eukaryotic cells that are also found in most biological fluids and tissues. While they were initially thought to act as compartments for removal of cellular debris, they are now recognized as important tools for cell-to-cell communication and for the transfer of pathogens between the cells. They have attracted particular interest in neurodegenerative diseases for their potential role in transferring prion-like proteins between neurons, and in Parkinson’s disease (PD), they have been shown to spread oligomers of α-synuclein in the brain accelerating the progression of this pathology. A potential neuroprotective role of exosomes has also been equally proposed in PD as they could limit the toxicity of α-synuclein by clearing them out of the cells. Exosomes have also attracted considerable attention for use as drug vehicles. Being nonimmunogenic in nature, they provide an unprecedented opportunity to enhance the delivery of incorporated drugs to target cells. In this review, we discuss current knowledge about the potential neurotoxic and neuroprotective role of exosomes and their potential application as drug delivery systems in PD.

scholarly journals Evolving Role of Microparticles in the Pathophysiology of Endothelial Dysfunction

2013 ◽  
Vol 59 (8) ◽  
pp. 1166-1174 ◽  
Author(s):  
Fina Lovren ◽  
Subodh Verma
Keyword(s):  
Endothelial Cells ◽  
Cardiovascular Diseases ◽  
Endothelial Dysfunction ◽  
Vascular Endothelial Cells ◽  
Current Knowledge ◽  
Early Event ◽  
Prognostic Information ◽  
Vascular Events ◽  
Wide Range

BACKGROUND Endothelial dysfunction is an early event in the development and progression of a wide range of cardiovascular diseases. Various human studies have identified that measures of endothelial dysfunction may offer prognostic information with respect to vascular events. Microparticles (MPs) are a heterogeneous population of small membrane fragments shed from various cell types. The endothelium is one of the primary targets of circulating MPs, and MPs isolated from blood have been considered biomarkers of vascular injury and inflammation. CONTENT This review summarizes current knowledge of the potential functional role of circulating MPs in promoting endothelial dysfunction. Cells exposed to different stimuli such as shear stress, physiological agonists, proapoptotic stimulation, or damage release MPs, which contribute to endothelial dysfunction and the development of cardiovascular diseases. Numerous studies indicate that MPs may trigger endothelial dysfunction by disrupting production of nitric oxide release from vascular endothelial cells and subsequently modifying vascular tone. Circulating MPs affect both proinflammatory and proatherosclerotic processes in endothelial cells. In addition, MPs can promote coagulation and inflammation or alter angiogenesis and apoptosis in endothelial cells. SUMMARY MPs play an important role in promoting endothelial dysfunction and may prove to be true biomarkers of disease state and progression.

scholarly journals Role of Differentiation of Liver Sinusoidal Endothelial Cells in Progression and Regression of Hepatic Fibrosis in Rats

2012 ◽  
Vol 142 (4) ◽  
pp. 918-927.e6 ◽  
Author(s):  
Guanhua Xie ◽  
Xiangdong Wang ◽  
Lei Wang ◽  
Lin Wang ◽  
Roscoe D. Atkinson ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Hepatic Fibrosis ◽  
Liver Sinusoidal Endothelial Cells ◽  
Sinusoidal Endothelial Cells

scholarly journals Interspecies Communication in Holobionts by Non-Coding RNA Exchange

2020 ◽  
Vol 21 (7) ◽  
pp. 2333
Author(s):  
Ana Lúcia Leitão ◽  
Marina C. Costa ◽  
André F. Gabriel ◽  
Francisco J. Enguita
Keyword(s):  
Target Cell ◽  
Current Knowledge ◽  
Cell Communication ◽  
Special Focus ◽  
Interspecies Communication ◽  
Communication Signals ◽  
Non Coding Rna ◽  
Molecular Machinery ◽  
Non Coding Rnas

Complex organisms are associations of different cells that coexist and collaborate creating a living consortium, the holobiont. The relationships between the holobiont members are essential for proper homeostasis of the organisms, and they are founded on the establishment of complex inter-connections between all the cells. Non-coding RNAs are regulatory molecules that can also act as communication signals between cells, being involved in either homeostasis or dysbiosis of the holobionts. Eukaryotic and prokaryotic cells can transmit signals via non-coding RNAs while using specific extracellular conveyors that travel to the target cell and can be translated into a regulatory response by dedicated molecular machinery. Within holobionts, non-coding RNA regulatory signaling is involved in symbiotic and pathogenic relationships among the cells. This review analyzes current knowledge regarding the role of non-coding RNAs in cell-to-cell communication, with a special focus on the signaling between cells in multi-organism consortia.

Molecular Characterization of F8 Secreting Cell

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4671-4671
Author(s):  
Osman El-Maarri ◽  
Muhammad Ahmer Jamil ◽  
Behnaz Pezeshkpoor ◽  
Nicole Nüsgen ◽  
Andrea Hofmann ◽  
...  
Keyword(s):  
Pattern Recognition ◽  
Endothelial Cells ◽  
Molecular Signature ◽  
Organ Specificity ◽  
Liver Sinusoidal Endothelial Cells ◽  
Total Blood ◽  
Genome Wide ◽  
Vessel Development ◽  
Signaling Activation

Abstract Different endothelial cells share common features but also acquire organ specificity: for example the liver sinusoidal endothelial cells (LSECs) are major site of F8 secretion as compared to other endothelial cells. To decipher this specificity in LSECs and to understand the molecular mechanism of F8 synthesis and secretion, we have compared genome wide expression and epigenetic data of fetal LSECs (N=3) and non-liver endothelial cells (HCMEC, HPAEC, HPMEC and HUVEC; N=3), hepatocytes (N=3) and adult total blood (N=3). At a false discovery rate of <5% we found 4134 differentially methylated CpG sites and 663 differentially expressed probes (corresponding to 623 genes/loci) between LSECs and other endothelial cells. The loci were found by ingenuity pathway analysis (IPA) to be enriched in EIF2, eIF4, p7056K and mTOR signaling pathways together with LXR/RXR activation pathway. On the other hand, only 21 different loci and 152 CpGs were found to be statistically different (at <5% FDR) between hepatocytes and LSECs. According to IPA these were found enriched in interferon signaling, activation of IRF by cytosolic pattern recognition receptors and role of pattern recognition receptor in recognition of bacteria and viruses. Additionally, gene ontology analysis showed enrichment in GO-terms such as regulation of cellular metabolic process for LSECs vs. endothelial cells and blood vessel development, cell adhesion and regulation of cell migration for LSECs vs. hepatocytes. Moreover, in each of the GO sub categories of general coagulation (GO:0007596) and transcription factors (GO:003700) a small number of loci successfully differentially identify the LSECs from other endothelial cells. The above described results show specific molecular signature that characterize the F8 secreting cells and highlight specific cellular pathways associated with this process. Disclosures Oldenburg: SOBI: Consultancy.

scholarly journals Inhibition of liver sinusoidal endothelial cells in rats with hepatic fibrosis by injection of VEGF 165 via the inferior vena cava

2021 ◽  
Author(s):  
Zhigang Sun ◽  
Tianyi Dong ◽  
Zhun Zhang ◽  
Tiantian Wang ◽  
Chenyu Zhang ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Transmission Electron Microscopy ◽  
Endothelial Cells ◽  
Liver Fibrosis ◽  
Serum Level ◽  
Basement Membranes ◽  
Liver Sinusoidal Endothelial Cells ◽  
Sinusoidal Endothelial Cells ◽  
Transmission Electron

Abstract Background Although VEGF can maintain the normal phenotype of liver sinusoidal endothelial cells (LSECs), it has also been reported that VEGF exacerbates cirrhosis. The role of VEGF in the progression and recovery of cirrhosis has still remained controversial.Methods We established a cirrhotic rat model by thioacetamide that was used as drinking water; besides, 0, 1, 2, and 4 μg VEGF165 were then continuously injected into the rats. The serum level of hyaluronic acid was measured by ELISA at 0, 1, and 4 weeks, separately. Serum levels of ALT, AST, direct bilirubin, indirect bilirubin, and ALB were detected by an automatic biochemical analyzer. In addition, the levels of VEGF165, CD44, MMP9, MMP2, HIF-1α, and endothelin were detected by Western blotting. The expression level of CD44 in LSECs was detected by immunohistochemistry. Changes of fenestrations of LSECs and basement membranes of blood vessels were observed by transmission electron microscopy. Results With the increase of dosage and duration of VEGF treatment, the levels of liver function markers in the serum, the levels of CD44, HIF-1α, hydroxyproline and endothelin were significantly improved. With determination of the serum level of hydroxyproline in the blood, it was disclosed that the mentioned level was markedly decreased. In the Sirius Red staining, the stained red area was gradually reduced. Images captured by transmission electron microscopy also confirmed that the ultrastructure of LSECs tended to be normal.Conclusion VEGF165 can accelerate the resolution of liver fibrosis by promoting fenestration structure formation in LSECs, as well as promoting material exchange between sinusoids and hepatocytes. Our findings may provide a new insight for the study of the role of VEGF in liver fibrosis.

scholarly journals MiRNAs in the Peri-Implantation Period: Contribution to Embryo–Maternal Communication in Pigs

2020 ◽  
Vol 21 (6) ◽  
pp. 2229 ◽  
Author(s):  
Monika M. Kaczmarek ◽  
Joanna Najmula ◽  
Maria M. Guzewska ◽  
Emilia Przygrodzka
Keyword(s):  
Current Knowledge ◽  
Mammalian Species ◽  
Embryo Implantation ◽  
Cell Communication ◽  
Large Family ◽  
Protein Coding ◽  
The Past ◽  
Domestic Livestock ◽  
Implantation Period

MicroRNAs (miRNAs) constitute a large family of noncoding RNAs, approximately 22 nucleotides long, which function as guide molecules in RNA silencing. Targeting most protein-coding transcripts, miRNAs are involved in nearly all developmental and pathophysiological processes in animals. To date, the regulatory roles of miRNAs in reproduction, such as fertilization, embryo development, implantation, and placenta formation, among others, have been demonstrated in numerous mammalian species, including domestic livestock such as pigs. Over the past years, it appeared that understanding the functions of miRNAs in mammalian reproduction can substantially improve our understanding of the biological challenges of successful reproductive performance. This review describes the current knowledge on miRNAs, specifically in relation to the peri-implantation period when the majority of embryonic mortality occurs in pigs. To present a broader picture of crucial peri-implantation events, we focus on the role of miRNA-processing machinery and miRNA–mRNA infarctions during the maternal recognition of pregnancy, leading to maintenance of the corpus luteum function and further embryo implantation. Furthermore, we summarize the current knowledge on cell-to-cell communication involving extracellular vesicles at the embryo–maternal interface in pigs. Finally, we discuss the potential of circulating miRNAs to serve as indicators of ongoing embryo–maternal crosstalk.

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