ADAMTS2 and ADAMTS14 can substitute for ADAMTS3 in adults for pro-VEGFC activation and lymphatic homeostasis.

The capacity of ADAMTS3 to cleave pro-VEGFC into active VEGFC able to bind its receptors and to stimulate lymphangiogenesis has been clearly established during embryonic life. However, this function of ADAMTS3 is unlikely to persist in adulthood because of its restricted expression pattern after birth. Because ADAMTS2 and ADAMTS14 are closely related to ADAMTS3 and are mainly expressed in connective tissues where the lymphatic network extends, we hypothesized that they could substitute for ADAMTS3 during adulthood in mammals allowing proteolytic activation of pro-VEGFC.

Purification of Native or Recombinant ADAMTS2, and Procollagen I Cleavage Assay.

ADAMTS constitute a family of 19 secreted metalloproteinases involved in diverse physiopathological conditions. Most of their roles first emerged from analysis of spontaneous human and animal mutations or genetically engineered animals. However, the involved mechanisms and the full repertoire of their functions are still largely unrecognized, in part because they are difficult to produce and purify as recombinant active enzymes.

Challenges and Solutions for Purification of ADAMTS Proteases: An Overview.

ADAMTS are secreted metalloproteinases implicated in many key biological processes. The 19 different members of this family share an identical domain composition at the level of their amino-terminal portion, whereas the identity and number of the domains forming their carboxy-terminal half are divergent and define distinct ADAMTS subfamilies. Due to their large size, extensive glycosylation, the presence of specific domains, their tendency to form aggregates, their relatively low abundance in tissues and the presence of many disulfide bonds, ADAMTS are very hard to isolate, express, and purify, as either native or recombinant active enzymes.

Propranolol sensitizes prostate cancer cells to glucose metabolism inhibition and prevents cancer progression.

Propranolol, a widely used non-selective beta-adrenergic receptor blocker, was recently shown to display anticancer properties. Its potential to synergize with certain drugs has been also outlined. However, it is necessary to take into account all the properties of propranolol to select a drug that could be efficiently combined with.

Chemotherapy induces alternative transcription and splicing: Facts and hopes for cancer treatment.

Alternative promoter usage, alternative splicing and alternative cleavage/polyadenylation (referred here as to alternative transcription and splicing) are main instruments to diversify the transcriptome from a limited set of genes. There is a good deal of evidence that chemotherapeutic drugs affect these processes, but the therapeutic incidence of these effects is poorly documented. The scope of this study is to review the impact of chemotherapy on alternative transcription and splicing and to discuss potential implications in cancer therapy.

Circulating microRNAs signature correlates with positive [F]fluorodeoxyglucose-positron emission tomography in patients with abdominal aortic aneurysm.

Background: Prediction of abdominal aortic aneurysm (AAA) rupture is a challenging issue. Small noncoding microRNAs (miRNAs) are potent regulators of gene expression and are considered as valuable circulating biomarkers. Recently, [F]fluorodeoxyglucose (FDG) uptake detected by positron emission tomography (PET) in AAA was correlated with cellular and molecular alterations involved in wall instability and its potential rupture.

Lipin-1 regulates cancer cell phenotype and is a potential target to potentiate rapamycin treatment.

Lipogenesis inhibition was reported to induce apoptosis and repress proliferation of cancer cells while barely affecting normal cells. Lipins exhibit dual function as enzymes catalyzing the dephosphorylation of phosphatidic acid to diacylglycerol and as co-transcriptional regulators. Thus, they are able to regulate lipid homeostasis at several nodal points.

Gene expression study in positron emission tomography-positive abdominal aortic aneurysms identifies CCL18 as a potential biomarker for rupture risk.

Rupture of abdominal aortic aneurysm (AAA) is a cause of significant mortality and morbidity in aging populations. Uptake of 18-fluorodeoxyglucose (FDG) detected by positron emission tomography (PET) is observed in the wall of 12% of AAA (A+), with most of them being symptomatic. We previously showed that the metabolically active areas displayed adventitial inflammation, medial degeneration and molecular alterations prefacing wall rupture.

Tgfβ-Smad and MAPK signaling mediate scleraxis and proteoglycan expression in heart valves.

Mature heart valves are complex structures consisting of three highly organized extracellular matrix layers primarily composed of collagens, proteoglycans and elastin. Collectively, these diverse matrix components provide all the necessary biomechanical properties for valve function throughout life. In contrast to healthy valves, myxomatous valve disease is the most common cause of mitral valve prolapse in the human population and is characterized by an abnormal abundance of proteoglycans within the valve tri-laminar structure.

18F-FDG uptake assessed by PET/CT in abdominal aortic aneurysms is associated with cellular and molecular alterations prefacing wall deterioration and rupture.

Unlabelled: Rupture of abdominal aortic aneurysms (AAAs) leads to a significant morbidity and mortality in aging populations, and its prediction would be most beneficial to public health. Spots positive for uptake of (18)F-FDG detected by PET are found in 12% of AAA patients (PET+), who are most often symptomatic and at high rupture risk. Comparing the (18)F-FDG-positive site with a negative site from the same aneurysm and with samples collected from AAA patients with no (18)F-FDG uptake should allow the discrimination of biologic alterations that would help in identifying markers predictive of rupture.

Effects of mild cold shock (25°C) followed by warming up at 37°C on the cellular stress response.

Temperature variations in cells, tissues and organs may occur in a number of circumstances. We report here that reducing temperature of cells in culture to 25°C for 5 days followed by a rewarming to 37°C affects cell biology and induces a cellular stress response. Cell proliferation was almost arrested during mild hypothermia and not restored upon returning to 37°C.

Dissection of Iliac Artery in a Patient With Autosomal Dominant Polycystic Kidney Disease: A Case Report.

Autosomal dominant polycystic kidney disease (ADPKD) is a risk factor for several cardiovascular disorders such as intracranial aneurysm or aortic dissection, preferentially occurring at the thoracic or abdominal level. A 47-year-old man suffering from ADPKD had renal transplantation. Sixteen hours after surgery, he presented with left leg pain.

Rho proteins crosstalk via RhoGDIalpha: At random or hierarchically ordered?

The small GTPases of the Rho family are key signaling molecules regulating a plethora of biological pathways. They can exert diverse, sometimes opposite, contributions to specific cellular processes explaining why their regulation and their crosstalk must be finely tuned. Several mechanisms driving crosstalk between Rho GTPases have been described in the literature.

Metallothionein-dependent up-regulation of TGF-β2 participates in the remodelling of the myxomatous mitral valve.

Aims: Although an excessive extracellular matrix remodelling has been well described in myxomatous mitral valve (MMV), the underlying pathogenic mechanisms remain largely unknown. Our goal was to identify dysregulated genes in human MMV and then to evaluate their functional role in the progression of the disease.

Methods And Results: Dysregulated genes were investigated by transcriptomic, immunohistochemistry, and western blot analyses of the P2 segment collected from human idiopathic MMV during valvuloplasty (n = 23) and from healthy control valves (n = 17).

RhoGDIα-dependent balance between RhoA and RhoC is a key regulator of cancer cell tumorigenesis.

RhoGTPases are key signaling molecules regulating main cellular functions such as migration, proliferation, survival, and gene expression through interactions with various effectors. Within the RhoA-related subclass, RhoA and RhoC contribute to several steps of tumor growth, and the regulation of their expression affects cancer progression. Our aim is to investigate their respective contributions to the acquisition of an invasive phenotype by using models of reduced or forced expression.

Alternative splicing: a promising target for pharmaceutical inhibition of pathological angiogenesis?

In eukaryotes, genes consist in coding sequences (exons) interspersed with non-coding ones (introns). The regulation of alternative inclusion/exclusion of exons, or part of exons, during the maturation of the pre-mRNA into mRNA (alternative splicing) allows a dramatic increase of the protein versus the gene repertoire. In a number of cases, alternative splicing decision generates proteins with distinct, sometimes opposite, functions from a given gene.

Newly identified biologically active and proteolysis-resistant VEGF-A isoform VEGF111 is induced by genotoxic agents.

Ultraviolet B and genotoxic drugs induce the expression of a vascular endothelial growth factor A (VEGF-A) splice variant (VEGF111) encoded by exons 1-4 and 8 in many cultured cells. Although not detected in a series of normal human and mouse tissue, VEGF111 expression is induced in MCF-7 xenografts in nude mice upon treatment by camptothecin. The skipping of exons that contain proteolytic cleavage sites and extracellular matrix-binding domains makes VEGF111 diffusible and resistant to proteolysis.

Regulation of procollagen amino-propeptide processing during mouse embryogenesis by specialization of homologous ADAMTS proteases: insights on collagen biosynthesis and dermatosparaxis.

Mutations in ADAMTS2, a procollagen amino-propeptidase, cause severe skin fragility, designated as dermatosparaxis in animals, and a subtype of the Ehlers-Danlos syndrome (dermatosparactic type or VIIC) in humans. Not all collagen-rich tissues are affected to the same degree, which suggests compensation by the ADAMTS2 homologs ADAMTS3 and ADAMTS14. In situ hybridization of Adamts2, Adamts3 and Adamts14, and of the genes encoding the major fibrillar collagens, Col1a1, Col2a1 and Col3a1, during mouse embryogenesis, demonstrated distinct tissue-specific, overlapping expression patterns of the protease and substrate genes.

Acidic extracellular pH induces matrix metalloproteinase-9 expression in mouse metastatic melanoma cells through the phospholipase D-mitogen-activated protein kinase signaling.

The extracellular pH (pHe) of tumor tissues is often acidic, which can induce the expression of several proteins. We previously showed that production of matrix metalloproteinase-9 (MMP-9) was induced by culturing cells at acidic pHe (5.4-6.