Endostatin, soluble tumour necrosis factor receptor 1 and soluble tumour necrosis factor receptor 2 cannot predict new onset of microalbuminuria in patients with type 2 diabetes.

Aims: Inflammation and angiogenesis play an important role in the development of early diabetic kidney disease. We investigated the association of soluble Tumour Necrosis Factor Receptor 1 (sTNF-R1), sTNF-R2 and endostatin with new onset microalbuminuria in normoalbuminuric patients with diabetes mellitus type 2.

Methods: We conducted a case control study to assess serum levels of sTNF-R1, sTNF-R2 and endostatin in 169 patients with new onset microalbuminuria and in 188 matched normoalbuminuric, diabetic controls.

Cold Shock Domain Protein DbpA Orchestrates Tubular Cell Damage and Interstitial Fibrosis in Inflammatory Kidney Disease.

DNA-binding protein A (DbpA) belongs to the Y-box family of cold shock domain proteins that exert transcriptional and translational activities in the cell via their ability to bind and regulate mRNA. To investigate the role of DbpA in kidney disease, we utilized the murine unilateral ureter obstruction (UUO) model, which recapitulates many features of obstructive nephropathy seen in humans. We observed that DbpA protein expression is induced within the renal interstitium following disease induction.

Midkine release during hemodialysis is predictive of hypervolemia and associates with excess (cardiovascular) mortality in patients with end-stage renal disease: a prospective study.

Background: In end-stage renal disease, a high cardiovascular risk profile and endothelial damage prevails. The heparin-binding growth factor midkine stimulates neo-angiogenesis in ischemic diseases, coordinates neutrophil influx, and raises blood pressure through stimulated angiotensin synthesis.

Methods: We determined changes of midkine serum levels during hemodialysis sessions under the assumption that endothelial cell-derived midkine is released.

Monocyte chemoattractant protein-1 predicts the development of diabetic nephropathy.

Aim: Diabetic nephropathy (DN) is a devastating complication of diabetes mellitus (DM). Therefore, screening strategies in order to prevent its development and/or retard its progression are of paramount importance. We investigated if monocyte chemoattractant protein-1 (MCP-1) was associated with new onset microalbuminuria-the earliest sign of the albuminuric phenotype of DN- in patients with type 2 DM and normoalbuminuria.

High salt diet-induced proximal tubular phenotypic changes and sodium-glucose cotransporter-2 expression are coordinated by cold shock Y-box binding protein-1.

High salt diet (HSD) is a hallmark of blood pressure elevations, weight gain and diabetes onset in the metabolic syndrome. In kidney, compensatory mechanisms are activated to balance salt turnover and maintain homeostasis. Data on the long-term effects of HSD with respect to tubular cell functions and kidney architecture that exclude confounding indirect blood pressure effects are scarce.

Fibrosis and Immune Cell Infiltration Are Separate Events Regulated by Cell-Specific Receptor Notch3 Expression.

Background: Kidney injuries that result in chronic inflammation initiate crosstalk between stressed resident cells and infiltrating immune cells. In animal models, whole-body receptor deficiency protects from leukocyte infiltration and organ fibrosis. However, the relative contribution of expression in tissue versus infiltrating immune cells is unknown.

Systemic Inflammation Precedes Microalbuminuria in Diabetes.

Aim: The aim of the case-control study was to investigate if serum biomarkers indicative of vascular inflammation and endothelial dysfunction can predict the development of microalbuminuria in patients with diabetes mellitus type 2.

Methods: Among participants enrolled in the ROADMAP (Randomized Olmesartan And Diabetes MicroAlbuminuria Prevention) and observational follow-up (OFU) studies, a panel of 15 serum biomarkers was quantified from samples obtained at initiation of the study and tested for associations with the development of new-onset microalbuminuria during follow-up. A case-control study was conducted with inclusion of 172 patients with microalbuminuria and 188 matched controls.

Crosstalk between Akt signaling and cold shock proteins in mediating invasive cell phenotypes.

Cold shock proteins are up-regulated by cellular stress and orchestrate inflammatory responses, cell proliferation, and differentiation. Enhanced cold shock protein expression promotes malignant cell transformation; up-regulation is detected in most cancers and associated with poor prognosis. Akt1, a serine/threonine kinase, is a potent oncogene, which activates pro-proliferative and anti-apoptotic signaling pathways, and phosphorylates the cold shock domain.

Inflammatory cell infiltration and resolution of kidney inflammation is orchestrated by the cold-shock protein Y-box binding protein-1.

Tubular cells recruit monocytic cells in inflammatory tubulointerstitial kidney diseases. The cell-cell communication that establishes pro- or anti-inflammatory activities is mainly influenced by cytokines, reactive oxygen species, nitric oxide, and phagocytosis. Key proteins orchestrating these processes such as cold-shock proteins linked with chemoattraction and cell maturation have been identified.

The role of cold shock domain proteins in inflammatory diseases.

Cold shock domain proteins are characterized by the presence of one or more evolutionarily conserved cold shock domains, which each possess two nucleic acid-binding motifs. These proteins exert pleiotropic functions in cells via their ability to bind single-stranded RNA and/or DNA, thus allowing them to serve as transcriptional as well as translational regulators. Not only can they regulate their own expression, but they also regulate the expression of a number of pro- and anti-inflammatory cytokines, as well as cytokine receptors, making them key players in the orchestration of inflammatory processes and immune cell phenotypes.

Induction of premalignant host responses by cathepsin x/z-deficiency in Helicobacter pylori-infected mice.

Helicobacter pylori are responsible for the induction of chronic gastric inflammation progressing to atrophy, metaplasia, and gastric cancer. The overexpression of Cathepsin X/Z (Ctsz) in H. pylori-infected mucosa and gastric cancer is mediated predominantly by an augmented migration of ctsz(-/-)positive macrophages and the up-regulation of Ctsz in tumor epithelium.

Cathepsin X-deficient gastric epithelial cells in co-culture with macrophages: characterization of cytokine response and migration capability after Helicobacter pylori infection.

Our previous studies have shown an association between Helicobacter pylori infection, the strong up-regulation of cathepsin X (CTSX, also called cathepsin Z/P), and the development of gastric cancer. In the present study, we analyzed primary and conventional gastric epithelial cell lines to establish an optimal in vitro mouse model system for the examination of H. pylori-induced overexpression of Ctsx in a functional way.

Regulation of cathepsin X overexpression in H. pylori-infected gastric epithelial cells and macrophages.

Cathepsin X (CTSX) is strongly up-regulated in Helicobacter pylori-infected gastric mucosa and intestinal-type gastric cancer. The overexpression of CTSX is mediated predominantly by associated macrophages; depends on a functional type IV-secretion system; and leads to increased migration of gastric epithelial cells. In the present study, we analysed the role of CagA in CTSX overexpression and identified H.