sodium azide in commercially available c reactive protein preparations does not influence matrix metalloproteinase 2 synthesis and release in cultured human aortic vascular smooth muscle cells

Detection of circulating concentrations of the acute-phase reactant C-reactive protein (CRP), which is synthesized in response to proinflammatory cytokines, is a relevant tool for identifying the involvement of low-grade inflammation in atherosclerosis and for predicting future atherothrombotic events (1). Whether CRP is only a marker or is also an active player in atherosclerotic injury is a matter of intense debate (2). CRP is present in atherosclerotic lesions (3) and can contribute directly to atherothrombosis (4). In particular, CRP induces expression of proatherogenetic molecules in endothelial cells and promotes LDL uptake by macrophages (4). We recently observed that CRP increases synthesis and secretion of matrix metalloproteinase 2 (MMP-2) from cultured human vascular smooth muscle cells (hVSMCs) (5), a mechanism potentially involved in plaque destabilization. Recently, however, the reliability of results concerning CRP obtained in vitro has been

TFEB controls integrin-mediated endothelial cell adhesion by the regulation of cholesterol metabolism

The dynamic integrin-mediated adhesion of endothelial cells (ECs) to the surrounding ECM is fundamental for angiogenesis both in physiological and pathological conditions, such as embryonic development and cancer progression. The dynamics of EC-to-ECM adhesions relies on the regulation of the conformational activation and trafficking of integrins. Here, we reveal that oncogenic transcription factor EB (TFEB), a known regulator of lysosomal biogenesis and metabolism, also controls a transcriptional program that influences the turnover of ECM adhesions in ECs by regulating cholesterol metabolism. We show that TFEB favors ECM adhesion turnover by promoting the transcription of genes that drive the synthesis of cholesterol, which promotes the aggregation of caveolin-1, and the caveolin-dependent endocytosis of integrin β1. These findings suggest that TFEB might represent a novel target for the pharmacological control of pathological angiogenesis and bring new insights in the mechanism sustaining TFEB control of endocytosis. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10456-022-09840-x

TFEB Signalling-Related MicroRNAs and Autophagy

The oncogenic Transcription Factor EB (TFEB), a member of MITF-TFE family, is known to be the most important regulator of the transcription of genes responsible for the control of lysosomal biogenesis and functions, autophagy, and vesicles flux. TFEB activation occurs in response to stress factors such as nutrient and growth factor deficiency, hypoxia, lysosomal stress, and mitochondrial damage. To reach the final functional status, TFEB is regulated in multimodal ways, including transcriptional rate, post-transcriptional regulation, and post-translational modifications. Post-transcriptional regulation is in part mediated by miRNAs. miRNAs have been linked to many cellular processes involved both in physiology and pathology, such as cell migration, proliferation, differentiation, and apoptosis. miRNAs also play a significant role in autophagy, which exerts a crucial role in cell behaviour during stress or survival responses. In particular, several miRNAs directly recognise TFEB transcript or indirectly regulate its function by targeting accessory molecules or enzymes involved in its post-translational modifications. Moreover, the transcriptional programs triggered by TFEB may be influenced by the miRNA-mediated regulation of TFEB targets. Finally, recent important studies indicate that the transcription of many miRNAs is regulated by TFEB itself. In this review, we describe the interplay between miRNAs with TFEB and focus on how these types of crosstalk affect TFEB activation and cellular functions