bims-stacyt 2019-03-10 papers

Endocrinol Diabetes Nutr. 2019 Mar 01. pii: S2530-0164(19)30032-1. [Epub ahead of print]

Inflammatory stress and altered angiogenesis evoked by very high-fat diets in mouse liver.

Adrián Plaza, Víctor Naranjo, Alessandra M Blonda, Victoria Cano, Carmen González-Martín, Marta Gil-Ortega, Mariano Ruiz-Gayo, Beatriz Merino.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD), a condition that leads to fibrosis, is caused by intake of very high-fat diets (HFDs). However, while the negative impact on the liver of these diets has been an issue of interest, systematic research on the effect of HFDs are lacking.
OBJECTIVE: To characterize the overall impact of HFDs on both molecular and morphological signs of liver remodeling.
METHODS: A study was conducted on male C57BL/6J mice to assess the effect of 4- and 8-week HFDs (60% kcal from fat) on (i) liver steatosis and fibrosis, and (ii) expression of factors involved in inflammation and angiogenesis.
RESULTS: After an 8-week HFD, vascular endothelial growth factor type-2 receptor (VEGF-R2) and fatty acid translocase/trombospondin-1 receptor (CD36) were overexpressed in liver tissue of mice given HFDs. These changes suggest impaired liver angiogenesis and occurred together with (i) increased GPR78-BiP and EIF2α phosphorylation, suggesting endoplasmic reticulum stress, (ii) induction of Col1a1 gene expression, a marker of fibrosis, and (iii) increased CD31 immunolabeling, consistent with active angiogenesis and fibrosis.
CONCLUSION: Our data show that very HFDs promote a rapid inflammatory response, as well as deregulation of angiogenesis, both consistent with development of liver fibrosis.

Keywords: CD36; Endoplasmic reticulum stress; Estrés del retículo endoplásmico; FCVE; Fibrosis hepática; Liver fibrosis; Obesidad; Obesity; VEGF

DOI: https://doi.org/10.1016/j.endinu.2018.12.009

Methods Mol Biol. 2019 ;1944 203-220

Tumorigenic Interplay Between Macrophages and Collagenous Matrix in the Tumor Microenvironment.

Chen Varol.

The tumor microenvironment is a heterogeneous tissue that in addition to tumor cells, contain tumor-associated cell types such as immune cells, fibroblasts, and endothelial cells. Considerably important in the tumor microenvironment is its noncellular component, namely, the extracellular matrix (ECM). In particular, the collagenous matrix is subjected to significant alterations in its composition and structure that create a permissive environment for tumor growth, invasion, and dissemination. Among tumor-infiltrating immune cells, tumor-associated macrophages (TAMs) are numerous in the tumor stroma and are locally educated to mediate important biological functions that profoundly affect tumor initiation, growth, and dissemination. While the influence of TAMs and mechanical properties of the collagenous matrix on tumor invasion and progression have been comprehensively investigated individually, their interaction within the complex tumor microenvironment was overlooked. This review summarizes accumulating evidence that indicate the existence of an intricate tumorigenic crosstalk between TAMs and collagenous matrix. A better mechanistic comprehension of this reciprocal interplay may open a novel arena for cancer therapeutics.

Keywords: Collagenous matrix; Tumor microenvironment; Tumor-associated macrophages

DOI: https://doi.org/10.1007/978-1-4939-9095-5_15

Immunobiology. 2019 Feb 22. pii: S0171-2985(19)30040-3. [Epub ahead of print]

Exosomes derived from monocytes and from endothelial cells mediate monocyte and endothelial cell activation under high d-glucose conditions.

Tamara Sáez, Paul de Vos, Jeroen Kuipers, Luis Sobrevia, Marijke M Faas.

Diabetes mellitus type 2 (DMT2) is characterized by hyperglycemia and associated with low grade inflammation affecting both endothelial cells and monocytes. Exosomes are nanovesicles, allow communication between endothelial cells and monocytes and have been associated with diabetic complications. In this study we evaluated whether high glucose can activate monocytes and endothelial cells and whether exosomes play a role in this activation. Moreover, we studied whether endothelial cells and monocytes communicate with each other via exosomes under high and basal glncubation. In the first experiment, monomac 6 cells (MM6) were exposed to high glucose (HG; 25 mmol/L) or to exosomes from MM6 exposed to HG (exoMM6-HG) or basal glucose (5.5 mmol/L) (exoMM6-BG). In the second experiment, MM6 were exposed to exosomes from human umbilical vein endothelial cells (HUVECs) and HUVECs to exosomes from MM6. In the third experiment, MM6 and HUVECs were exposed to a mixture of exosomes from MM6 and HUVECs (exoMix). Cell activation was evaluated by measuring the protein surface expression of intracellular adhesion molecule-1 (ICAM-1) by flow cytometry. HG increased ICAM-1 expression in MM6 and monocytic exosomes from HG or BG shown similar effect in HG and BG MM6 cells. Exosomes from HUVECs increased ICAM-1 expression in MM6 cells, incubated under HG or BG, while also exosomes from MM6 increased ICAM-1 expression in HUVECs incubated under HG or BG. The combination of exosomes from both cell types (exoMixHG or exoMixBG) also increased ICAM-1 expression in both type cells in most conditions. However, the exoMixBG reversed the effect of HG in both MM6 and HUVECs. Our results show that HG activated monocytes and endothelial cells and that exosomes play a role in this HG-induced cell ICAM-1 expression. We hypothesize that during DMT2, exosomes may act as a communication mechanism between monocytes and endothelial cells, inducing and maintaining activating of both cell types in the presence of high glucose.

Keywords: Diabetes mellitus type 2; Endothelial cells; Exosomes; Hyperglycemia; ICAM-1; Monocytes

DOI: https://doi.org/10.1016/j.imbio.2019.02.004