Nox and renal disease.

Since the first demonstration of Nox enzyme expression in the kidney in the early 1990s and the subsequent identification of Nox4, or RENOX, a decade later, it has become apparent that the Nox family of reactive oxygen species (ROS) generating enzymes plays an integral role in the normal physiological function of the kidney. As our knowledge of Nox expression patterns and functions in various structures and specialized cell types within the kidney grows, so does the realization that Nox-derived oxidative stress contributes significantly to a wide variety of renal pathologies through their ability to modify lipids and proteins, damage DNA and activate transcriptional programmes. Diverse studies demonstrate key roles for Nox-derived ROS in kidney fibrosis, particularly in settings of chronic renal disease such as diabetic nephropathy.

A novel mouse model of advanced diabetic kidney disease.

Currently available rodent models exhibit characteristics of early diabetic nephropathy (DN) such as hyperfiltration, mesangial expansion, and albuminuria yet features of late DN (hypertension, GFR decline, tubulointerstitial fibrosis) are absent or require a significant time investment for full phenotype development. Accordingly, the aim of the present study was to develop a mouse model of advanced DN with hypertension superimposed (HD mice). Mice transgenic for human renin cDNA under the control of the transthyretin promoter (TTRhRen) were employed as a model of angiotensin-dependent hypertension.

Ubiquitin C-terminal hydrolase L1 deletion ameliorates glomerular injury in mice with ACTN4-associated focal segmental glomerulosclerosis.

Renal ubiquitin C-terminal hydrolase L1 (UCHL1) is upregulated in a subset of human glomerulopathies, including focal segmental glomerulosclerosis (FSGS), where it may serve to promote ubiquitin pools for degradation of cytotoxic proteins. In the present study, we tested whether UCHL1 is expressed in podocytes of a mouse model of ACTN4-associated FSGS. Podocyte UCHL1 protein was detected in glomeruli of K256E-ACTN4(pod+)/UCHL1+/+ mice.

Microparticles induce cell cycle arrest through redox-sensitive processes in endothelial cells: implications in vascular senescence.

Background: Chronic disease accelerates endothelial dysfunction in aging, a process associated with cell senescence. However, the mechanisms underlying this process are unclear. We examined whether endothelial cell (EC)-derived microparticles (MPs) facilitate EC senescence and questioned the role of reactive oxygen species in this process.