Exploring the transcriptomic network of multi-ligand scavenger receptor Stabilin-1- and Stabilin-2-deficient liver sinusoidal endothelial cells.

The Class H scavenger receptors Stabilin-1 (Stab1) and Stabilin-2 (Stab2) are two of the most highly expressed genes in liver sinusoidal endothelial cells (LSECs). While Stab1-deficient (Stab1KO) and Stab2-deficient (Stab2KO) mice are phenotypically unremarkable, Stab1/2-double-deficient (StabDKO) mice exhibit perisinusoidal liver fibrosis, glomerulofibrotic nephropathy and a reduced life expectancy. These conditions are caused by insufficiently scavenged circulating noxious blood factors.

Time Series Analysis and Forecasting with Automated Machine Learning on a National ICD-10 Database.

The application of machine learning (ML) for use in generating insights and making predictions on new records continues to expand within the medical community. Despite this progress to date, the application of time series analysis has remained underexplored due to complexity of the underlying techniques. In this study, we have deployed a novel ML, called automated time series (AutoTS) machine learning, to automate data processing and the application of a multitude of models to assess which best forecasts future values.

Single-Cell RNA Sequencing of Tumor-Infiltrating NK Cells Reveals that Inhibition of Transcription Factor HIF-1α Unleashes NK Cell Activity.

Enhancing immune cell functions in tumors remains a major challenge in cancer immunotherapy. Hypoxia is a common feature of solid tumors, and cells adapt by upregulating the transcription factor HIF-1α. Here, we defined the transcriptional landscape of mouse tumor-infiltrating natural killer (NK) cells by using single-cell RNA sequencing.

Angiocrine Hepatocyte Growth Factor Signaling Controls Physiological Organ and Body Size and Dynamic Hepatocyte Proliferation to Prevent Liver Damage during Regeneration.

Liver sinusoidal endothelial cells (LSECs) control organ functions, metabolism, and development through the secretion of angiokines. LSECs express hepatocyte growth factor (Hgf), which is involved in prenatal development, metabolic homeostasis, and liver regeneration. This study aimed to elucidate the precise contribution of LSEC-derived Hgf in physiological homeostasis and liver regeneration.

Pianp deficiency links GABA receptor signaling and hippocampal and cerebellar neuronal cell composition to autism-like behavior.

Pianp (also known as Leda-1) is a type I transmembrane protein with preferential expression in the mammalian CNS. Its processing is characterized by proteolytic cleavage by a range of proteases including Adam10, Adam17, MMPs, and the γ-secretase complex. Pianp can interact with Pilrα and the GB1a subunit of the GABA receptor (GBR) complex.

Reconstruction of Nasal Defects With Dermal Skin Substitutes-A Retrospective Study of 36 Defects.

Objectives: It is uncertain whether dermal regeneration templates (DRTs) are helpful to reconstruct nasal defects. The aim of this study was to assess whether the aesthetic subunits determine the outcome.

Methods: In this unicentric, retrospective study, the surgical procedures and outcomes of patients who received DRTs to reconstruct nasal defects were assessed and compared with the involved aesthetic subunits.

Brg1 promotes liver regeneration after partial hepatectomy via regulation of cell cycle.

Brahma-related gene 1 (Brg1), a catalytic subunit of the SWItch/Sucrose Non-Fermentable (SWI/SNF) complex, is known to be involved in proliferative cell processes. Liver regeneration is initiated spontaneously after injury and leads to a strong proliferative response. In this study, a hepatocyte-specific Brg1 gene knockout mouse model was used to analyse the role of Brg1 in liver regeneration by performing a 70% partial hepatectomy (PH).

Hematopoietic Stabilin-1 deficiency does not influence atherosclerosis susceptibility in LDL receptor knockout mice.

Background And Aims: Stabilin-1 (STAB1) is a scavenger receptor expressed on alternatively activated macrophages and sinusoidal endothelial cells. Its ligands include oxidized low-density lipoprotein (LDL) and the extracellular matrix glycoprotein SPARC and it is present in both human and murine atherosclerotic lesions. We aimed to investigate the effect of specific deletion of STAB1 in bone marrow-derived cells, including macrophages on atherosclerotic lesion formation in mice.

Hepatic Endothelial Notch Activation Protects against Liver Metastasis by Regulating Endothelial-Tumor Cell Adhesion Independent of Angiocrine Signaling.

The interaction of tumor cells with organ-specific endothelial cells (EC) is an important step during metastatic progression. Notch signaling in organ-specific niches has been implicated in mediating opposing effects on organotropic metastasis to the lungs and the liver, respectively. In this study, we scrutinized the role of endothelial Notch activation during liver metastasis.

The novel immunoglobulin super family receptor SLAMF9 identified in TAM of murine and human melanoma influences pro-inflammatory cytokine secretion and migration.

Melanoma is a highly immunogenic tumor with a good response to treatment with immune checkpoint inhibitors. Tumor-associated macrophages (TAMs) play an important immunosuppressive role in such tumors and have therefore been identified as possible future therapeutic targets in oncology. The aim of this study was to identify novel immunoregulatory receptors specifically expressed on TAM.

GPR182 is a novel marker for sinusoidal endothelial differentiation with distinct GPCR signaling activity in vitro.

Endothelial cells (EC) along the vascular tree exhibit organ-specific angiodiversity. Compared to most other ECs, liver sinusoidal endothelial cells (LSEC) that constitute the organ-specific microvasculature of the liver are morphologically and functionally unique. Previously, we showed that transcription factor Gata4 acts as a master regulator controlling LSEC differentiation.

The shedded ectodomain of Lyve-1 expressed on M2-like tumor-associated macrophages inhibits melanoma cell proliferation.

Targeting immune cells that support tumor growth is an effective therapeutic strategy in tumor entities such as melanoma. M2-like tumor-associated macrophages (TAM) sustain tumor growth by secreting anti-inflammatory cytokines, proteases and growth factors. In this study, we show that a protein derived from M2-like macrophages namely the shedded ectodomain of Lyve-1 (sLyve-1) decreases human HT144 and murine B16F1 melanoma cell proliferation significantly by acting as a decoy receptor for low-molecular weight hyaluronic acid (LMW-HA) although the LMW-HA/Lyve-1 interaction on lymphatic endothelial cells has been described to induce lymphangiogenesis.

Angiocrine Wnt signaling controls liver growth and metabolic maturation in mice.

Unlabelled: Postnatal liver development is characterized by hepatocyte growth, proliferation, and functional maturation. Notably, canonical Wnt signaling in hepatocytes has been identified as an important regulator of final adult liver size and metabolic liver zonation. The cellular origin of Wnt ligands responsible for homeostatic liver/body weight ratio (LW/BW) remained unclear, which was also attributable to a lack of suitable endothelial Cre driver mice.

GATA4 and LMO3 balance angiocrine signaling and autocrine inflammatory activation by BMP2 in liver sinusoidal endothelial cells.

Liver sinusoidal endothelial cells (LSEC) represent a unique, organ-specific type of discontinuous endothelial cells. LSEC instruct the hepatic vascular niche by paracrine-acting angiocrine factors. Recently, we have shown that LSEC-specific transcriptional regulator GATA4 induces expression of BMP2 in cultured endothelial cells (EC) in vitro.

Angiocrine Bmp2 signaling in murine liver controls normal iron homeostasis.

Microvascular endothelial cells (ECs) display a high degree of phenotypic and functional heterogeneity among different organs. Organ-specific ECs control their tissue microenvironment by angiocrine factors in health and disease. Liver sinusoidal endothelial cells (LSECs) are uniquely differentiated to fulfill important organ-specific functions in development, under homeostatic conditions, and in regeneration and liver pathology.

Leda-1/Pianp is targeted to the basolateral plasma membrane by a distinct intracellular juxtamembrane region and modulates barrier properties and E-Cadherin processing.

Leda-1/Pianp is a type-I transmembrane protein which is sorted to the basolateral membrane domain of polarized epithelial cells. Here, we investigated trafficking mechanisms and functions of Leda-1/Pianp in MDCK and MCF-7 cells. Basolateral sorting and posttranslational modifications depended on the intracellular juxtamembrane region.

Angiogenesis in malignant melanoma.

Despite the development of novel therapies, the therapy of malignant melanoma remains challenging. Various studies have shown the vascular system to be pivotal for metastasis in melanoma. Consequently, the effect of various antiangiogenic therapies has been and is being investigated in preclinical and clinical trials.

TGF-β1, but not bone morphogenetic proteins, activates Smad1/5 pathway in primary human macrophages and induces expression of proatherogenic genes.

Macrophages are responsible for the control of inflammation and healing, and their malfunction results in cardiometabolic disorders. TGF-β is a pleiotropic growth factor with dual (protective and detrimental) roles in atherogenesis. We have previously shown that in human macrophages, TGF-β1 activates Smad2/3 signaling and induces a complex gene expression program.