scholarly journals Stromal cell-derived factor-1 (SDF-1) as a target in liver diseases

2016 ◽  
Vol 311 (2) ◽  
pp. G203-G209 ◽  
Author(s):  
Anke Liepelt ◽  
Frank Tacke
Keyword(s):  
Liver Injury ◽  
Chemokine Receptors ◽  
Liver Diseases ◽  
Stromal Cell ◽  
Current Knowledge ◽  
Suppressor Cells ◽  
Cancer Therapies ◽  
Liver Sinusoidal Endothelial Cells ◽  
Chronic Injury ◽  
Stromal Cell Derived Factor

The chemokine stromal cell-derived factor-1 (SDF-1) or CXCL12 is constitutively expressed in healthy liver. However, its expression increases following acute or chronic liver injury. Liver sinusoidal endothelial cells (LSEC), hepatic stellate cells (HSC), and malignant hepatocytes are important sources of SDF-1/CXCL12 in liver diseases. CXCL12 is able to activate two chemokine receptors with different downstream signaling pathways, CXCR4 and CXCR7. CXCR7 expression is relevant on LSEC, while HSC, mesenchymal stem cells, and tumor cells mainly respond via CXCR4. Here, we summarize recent developments in the field of liver diseases involving this chemokine and its receptors. SDF-1-dependent signaling contributes to modulating acute liver injury and subsequent tissue regeneration. By activating HSC and recruiting mesenchymal cells from bone marrow, CXCL12 can promote liver fibrosis progression, while CXCL12-CXCR7 interactions endorse proregenerative responses in chronic injury. Moreover, the SDF-1 pathway is linked to development of hepatocellular carcinoma (HCC) by promoting tumor growth, angiogenesis, and HCC metastasis. High hepatic CXCR4 expression has been suggested as a biomarker indicating poor prognosis of HCC patients. Tumor-infiltrating myeloid-derived suppressor cells (MDSC) also express CXCR4 and migrate toward CXCL12. Thus CXCL12 inhibition might not only directly block HCC growth but also modulate the tumor microenvironment (angiogenesis, MDSC), thereby sensitizing HCC patients to conventional or emerging novel cancer therapies (e.g., sorafenib, regorafenib, nivolumab, pembrolizumab). We herein summarize the current knowledge on the complex interplay between CXCL12 and CXCR4/CXCR7 in liver diseases and discuss approaches on the therapeutic targeting of these axes in hepatitis, fibrosis, and liver cancer.

scholarly journals PPARs in Liver Diseases and Cancer: Epigenetic Regulation by MicroRNAs

PPAR Research ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-16 ◽  
Author(s):  
Marion Peyrou ◽  
Pierluigi Ramadori ◽  
Lucie Bourgoin ◽  
Michelangelo Foti
Keyword(s):  
Liver Diseases ◽  
Metabolic Diseases ◽  
Viral Infections ◽  
Inflammatory Responses ◽  
Current Knowledge ◽  
Hepatocellular Adenoma ◽  
Peroxisome Proliferator ◽  
Cancer Therapies ◽  
Ppar Agonists ◽  
Expression And Activity

Peroxisome-proliferator-activated receptors (PPARs) are ligand-activated nuclear receptors that exert in the liver a transcriptional activity regulating a whole spectrum of physiological functions, including cholesterol and bile acid homeostasis, lipid/glucose metabolism, inflammatory responses, regenerative mechanisms, and cell differentiation/proliferation. Dysregulations of the expression, or activity, of specific PPAR isoforms in the liver are therefore believed to represent critical mechanisms contributing to the development of hepatic metabolic diseases, disorders induced by hepatic viral infections, and hepatocellular adenoma and carcinoma. In this regard, specific PPAR agonists have proven to be useful to treat these metabolic diseases, but for cancer therapies, the use of PPAR agonists is still debated. Interestingly, in addition to previously described mechanisms regulating PPARs expression and activity, microRNAs are emerging as new important regulators of PPAR expression and activity in pathophysiological conditions and therefore may represent future therapeutic targets to treat hepatic metabolic disorders and cancers. Here, we reviewed the current knowledge about the general roles of the different PPAR isoforms in common chronic metabolic and infectious liver diseases, as well as in the development of hepatic cancers. Recent works highlighting the regulation of PPARs by microRNAs in both physiological and pathological situations with a focus on the liver are also discussed.

Stromal cell–derived factor-1 and macrophage-derived chemokine: 2 chemokines that activate platelets

Blood ◽  
2000 ◽  
Vol 96 (1) ◽  
pp. 50-57 ◽  
Author(s):  
M. Anna Kowalska ◽  
Mariusz Z. Ratajczak ◽  
Marcin Majka ◽  
Jianguo Jin ◽  
Satya Kunapuli ◽  
...  
Keyword(s):  
Chemokine Receptors ◽  
Stromal Cell ◽  
Platelet Rich Plasma ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Creatine Phosphate ◽  
Polymerase Chain ◽  
Stromal Cell Derived Factor ◽  
Induced Aggregation ◽  
Second Wave

Platelets play roles in both thrombosis and inflammation, and chemokines that are released at sites of inflammation could potentially activate platelets. Among the chemokine receptors expressed on platelets, the CXCR4 is the receptor for chemokine stromal cell-derived factor-1 (SDF-1), and the CCR4 is the receptor for macrophage-derived chemokine (MDC). Of the chemokines tested, SDF-1 and MDC were the only 2 that activated platelets. Both are weak agonists, but they enhanced response to low-dose adenosine 5′-diphosphate (ADP), epinephrine, or serotonin. When SDF-1 and MDC were added together, full and brisk platelet aggregation occurred. Platelet activation by these 2 chemokines appears to involve distinct pathways: SDF-1 inhibited an increase in cyclic adenosine monophosphate (cAMP) following prostaglandin (PG) I2, while MDC had no effect. In contrast, MDC, but not SDF-1, lead to Ca++mobilization by platelets. Further, second-wave aggregation induced by MDC in platelet-rich plasma was inhibited by aspirin, ADP scavenger creatine phosphate/creative phosphokinase (CP/CPK), and ARL-66096, an antagonist of the ADP P2TAC receptor involved in adenylyl cyclase inhibition. But the aggregation was not affected by A3P5PS, an inhibitor of the ADP P2Y receptor. SDF-1–induced aggregation was inhibited by aspirin, but it was only slightly affected by CP/CPK, ARL-66096, or A3P5PS. Finally, the presence of chemokines in platelets was determined. Reverse transcriptase–polymerase chain reaction studies with platelet RNA did not detect the presence of SDF-1 or MDC. In summary, SDF-1 and MDC are platelet agonists that activate distinct intracellular pathways. Their importance in the development of thrombosis at sites of inflammation needs to be further evaluated.

scholarly journals Stromal Cell–Derived Factor-1 from Biliary Epithelial Cells Recruits CXCR4-Positive Cells: Implications for Inflammatory Liver Diseases

2003 ◽  
Vol 83 (5) ◽  
pp. 665-672 ◽  
Author(s):  
Ryo Terada ◽  
Kazuhide Yamamoto ◽  
Tomomi Hakoda ◽  
Noriaki Shimada ◽  
Nobuaki Okano ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Liver Diseases ◽  
Stromal Cell ◽  
Biliary Epithelial Cells ◽  
Stromal Cell Derived Factor

scholarly journals The Hepatic Sinusoid in Chronic Liver Disease: The Optimal Milieu for Cancer

Cancers ◽  
2021 ◽  
Vol 13 (22) ◽  
pp. 5719
Author(s):  
Albert Gibert-Ramos ◽  
David Sanfeliu-Redondo ◽  
Peio Aristu-Zabalza ◽  
Ana Martínez-Alcocer ◽  
Jordi Gracia-Sancho ◽  
...  
Keyword(s):  
Liver Disease ◽  
Chronic Liver Disease ◽  
Current Knowledge ◽  
Cell Types ◽  
Chronic Liver ◽  
Liver Sinusoidal Endothelial Cells ◽  
Chronic Injury ◽  
Unique Type ◽  
Sinusoidal Cells ◽  
Hepatic Sinusoid

The liver sinusoids are a unique type of microvascular beds. The specialized phenotype of sinusoidal cells is essential for their communication, and for the function of all hepatic cell types, including hepatocytes. Liver sinusoidal endothelial cells (LSECs) conform the inner layer of the sinusoids, which is permeable due to the fenestrae across the cytoplasm; hepatic stellate cells (HSCs) surround LSECs, regulate the vascular tone, and synthetize the extracellular matrix, and Kupffer cells (KCs) are the liver-resident macrophages. Upon injury, the harmonic equilibrium in sinusoidal communication is disrupted, leading to phenotypic alterations that may affect the function of the whole liver if the damage persists. Understanding how the specialized sinusoidal cells work in coordination with each other in healthy livers and chronic liver disease is of the utmost importance for the discovery of new therapeutic targets and the design of novel pharmacological strategies. In this manuscript, we summarize the current knowledge on the role of sinusoidal cells and their communication both in health and chronic liver diseases, and their potential pharmacologic modulation. Finally, we discuss how alterations occurring during chronic injury may contribute to the development of hepatocellular carcinoma, which is usually developed in the background of chronic liver disease.

scholarly journals Stromal-Cell-Derived Factor-1 (SDF-1)/CXCL12 as Potential Target of Therapeutic Angiogenesis in Critical Leg Ischaemia

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Teik K. Ho ◽  
X. Shiwen ◽  
D. Abraham ◽  
J. Tsui ◽  
D. Baker
Keyword(s):  
Skeletal Muscle ◽  
Chemokine Receptors ◽  
Stromal Cell ◽  
Therapeutic Angiogenesis ◽  
Limb Amputation ◽  
Western World ◽  
High Morbidity ◽  
Biologic Effects ◽  
Inflammatory Processes ◽  
Stromal Cell Derived Factor

In the Western world, peripheral vascular disease (PVD) has a high prevalence with high morbidity and mortality. In a large percentage of these patients, lower limb amputation is still required. Studies of ischaemic skeletal muscle disclosed evidence of endogenous angiogenesis and adaptive skeletal muscle metabolic changes in response to hypoxia. Chemokines are potent chemoattractant cytokines that regulate leukocyte trafficking in homeostatic and inflammatory processes. More than 50 different chemokines and 20 different chemokine receptors have been cloned. The chemokine stromal-cell-derived factor-1 (SDF-1 aka CXCL12) is a constitutively expressed and inducible chemokine that regulates multiple physiological processes, including embryonic development and organ homeostasis. The biologic effects of SDF-1 are mediated by chemokine receptor CXCR4, a 352 amino acid rhodopsin-like transmembrane-specific G protein-coupled receptor (GPCR). There is evidence that the administration of SDF-1 increases blood flow and perfusion via recruitment of endothelial progenitor cells (EPCs). This review will focus on the role of the SDF-1/CXCR4 system in the pathophysiology of PVD and discuss their potential as therapeutic targets for PVD.

scholarly journals The Influence of Chronic Liver Diseases on Hepatic Vasculature: A Liver-on-a-chip Review

Micromachines ◽  
2020 ◽  
Vol 11 (5) ◽  
pp. 487 ◽  
Author(s):  
Alican Özkan ◽  
Danielle Stolley ◽  
Erik N. K. Cressman ◽  
Matthew McMillin ◽  
Sharon DeMorrow ◽  
...  
Keyword(s):  
Liver Disease ◽  
Chronic Liver Disease ◽  
Liver Diseases ◽  
Recent Literature ◽  
Chronic Liver ◽  
Chronic Liver Diseases ◽  
Liver Sinusoidal Endothelial Cells ◽  
Chronic Injury ◽  
Hepatic Vasculature

In chronic liver diseases and hepatocellular carcinoma, the cells and extracellular matrix of the liver undergo significant alteration in response to chronic injury. Recent literature has highlighted the critical, but less studied, role of the liver vasculature in the progression of chronic liver diseases. Recent advancements in liver-on-a-chip systems has allowed in depth investigation of the role that the hepatic vasculature plays both in response to, and progression of, chronic liver disease. In this review, we first introduce the structure, gradients, mechanical properties, and cellular composition of the liver and describe how these factors influence the vasculature. We summarize state-of-the-art vascularized liver-on-a-chip platforms for investigating biological models of chronic liver disease and their influence on the liver sinusoidal endothelial cells of the hepatic vasculature. We conclude with a discussion of how future developments in the field may affect the study of chronic liver diseases, and drug development and testing.

scholarly journals Food and Nutrition in the Pathogenesis of Liver Damage

Nutrients ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 1326
Author(s):  
Andrea Mega ◽  
Luca Marzi ◽  
Michael Kob ◽  
Andrea Piccin ◽  
Annarosa Floreani
Keyword(s):  
Liver Injury ◽  
Environmental Factors ◽  
Liver Damage ◽  
Liver Diseases ◽  
Current Knowledge ◽  
Regulation Of Metabolism ◽  
Food And Nutrition ◽  
The Impact ◽  
Exogenous Substances

The liver is an important organ and plays a key role in the regulation of metabolism and in the secretion, storage, and detoxification of endogenous and exogenous substances. The impact of food and nutrition on the pathophysiological mechanisms of liver injury represents a great controversy. Several environmental factors including food and micronutrients are involved in the pathogenesis of liver damage. Conversely, some xenobiotics and micronutrients have been recognized to have a protective effect in several liver diseases. This paper offers an overview of the current knowledge on the role of xenobiotics and micronutrients in liver damage.

Stromal cell–derived factor-1 and macrophage-derived chemokine: 2 chemokines that activate platelets

Blood ◽  
2000 ◽  
Vol 96 (1) ◽  
pp. 50-57 ◽  
Author(s):  
M. Anna Kowalska ◽  
Mariusz Z. Ratajczak ◽  
Marcin Majka ◽  
Jianguo Jin ◽  
Satya Kunapuli ◽  
...  
Keyword(s):  
Chemokine Receptors ◽  
Stromal Cell ◽  
Platelet Rich Plasma ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Creatine Phosphate ◽  
Polymerase Chain ◽  
Stromal Cell Derived Factor ◽  
Induced Aggregation ◽  
Second Wave

Abstract Platelets play roles in both thrombosis and inflammation, and chemokines that are released at sites of inflammation could potentially activate platelets. Among the chemokine receptors expressed on platelets, the CXCR4 is the receptor for chemokine stromal cell-derived factor-1 (SDF-1), and the CCR4 is the receptor for macrophage-derived chemokine (MDC). Of the chemokines tested, SDF-1 and MDC were the only 2 that activated platelets. Both are weak agonists, but they enhanced response to low-dose adenosine 5′-diphosphate (ADP), epinephrine, or serotonin. When SDF-1 and MDC were added together, full and brisk platelet aggregation occurred. Platelet activation by these 2 chemokines appears to involve distinct pathways: SDF-1 inhibited an increase in cyclic adenosine monophosphate (cAMP) following prostaglandin (PG) I2, while MDC had no effect. In contrast, MDC, but not SDF-1, lead to Ca++mobilization by platelets. Further, second-wave aggregation induced by MDC in platelet-rich plasma was inhibited by aspirin, ADP scavenger creatine phosphate/creative phosphokinase (CP/CPK), and ARL-66096, an antagonist of the ADP P2TAC receptor involved in adenylyl cyclase inhibition. But the aggregation was not affected by A3P5PS, an inhibitor of the ADP P2Y receptor. SDF-1–induced aggregation was inhibited by aspirin, but it was only slightly affected by CP/CPK, ARL-66096, or A3P5PS. Finally, the presence of chemokines in platelets was determined. Reverse transcriptase–polymerase chain reaction studies with platelet RNA did not detect the presence of SDF-1 or MDC. In summary, SDF-1 and MDC are platelet agonists that activate distinct intracellular pathways. Their importance in the development of thrombosis at sites of inflammation needs to be further evaluated.

scholarly journals Role of Liver-Mediated Tolerance in Nanoparticle-Based Tumor Therapy

Cells ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 1985
Author(s):  
Maximiliano L. Cacicedo ◽  
Carolina Medina-Montano ◽  
Leonard Kaps ◽  
Cinja Kappel ◽  
Stephan Gehring ◽  
...  
Keyword(s):  
Hepatic Stellate Cells ◽  
Liver Diseases ◽  
Potential Role ◽  
Current Knowledge ◽  
Tumor Therapy ◽  
Stellate Cells ◽  
Liver Sinusoidal Endothelial Cells ◽  
Parenchymal Cells ◽  
Systemic Application

In the last decades, the use of nanocarriers for immunotherapeutic purposes has gained a lot of attention, especially in the field of tumor therapy. However, most types of nanocarriers accumulate strongly in the liver after systemic application. Due to the default tolerance-promoting role of liver non-parenchymal cells (NPCs), Kupffer cells (KCs), liver sinusoidal endothelial cells (LSECs), and hepatic stellate cells (HSCs), their potential role on the immunological outcome of systemic nano-vaccination approaches for therapy of tumors in the liver and in other organs needs to be considered. Concerning immunological functions, KCs have been the focus until now, but recent studies have elucidated an important role of LSECs and HSCs as well. Therefore, this review aims to summarize current knowledge on the employment of nanocarriers for immunotherapeutic therapy of liver diseases and the overall role of liver NPCs in the context of nano-vaccination approaches. With regard to the latter, we discuss strategies on how to address liver NPCs, aiming to exploit and modulate their immunological properties, and alternatively how to avoid unwanted engagement of nano-vaccines by liver NPCs for tumor therapy.

scholarly journals Myeloid-derived suppressor cells and their role in gynecological malignancies

Tumor Biology ◽  
2018 ◽  
Vol 40 (7) ◽  
pp. 101042831877648 ◽  
Author(s):  
Seiji Mabuchi ◽  
Eriko Yokoi ◽  
Naoko Komura ◽  
Tadashi Kimura
Keyword(s):  
Immune Responses ◽  
Current Knowledge ◽  
Gynecological Cancer ◽  
Suppressor Cells ◽  
Heterogeneous Population ◽  
Cancer Therapies ◽  
Myeloid Derived Suppressor Cells ◽  
Immunosuppressive Activity ◽  
Anti Cancer ◽  
Immature Myeloid Cells

Myeloid-derived suppressor cells are a heterogeneous population of immature myeloid cells that exhibit immunosuppressive activity (they block the proliferation and activity of both T cells and natural killer cells). In addition to their role in suppressing immune responses, myeloid-derived suppressor cells directly stimulate tumor cell proliferation, metastasis, and angiogenesis. In the area of gynecological cancer, increased numbers of circulating myeloid-derived suppressor cells or tumor-infiltrating myeloid-derived suppressor cells have been detected, and the increased frequencies of myeloid-derived suppressor cells are associated with a poor prognosis. Thus, the successful myeloid-derived suppressor cells depletion may hold the key to maximizing existing anti-cancer therapies and improving the prognosis of gynecological cancer. In this review, we summarize current knowledge regarding myeloid-derived suppressor cells biology, clinical significance of myeloid-derived suppressor cells, and the potential myeloid-derived suppressor cells–targeting strategies in gynecological cancer.

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