Effect of angiotensin type 2 receptor over-expression on the rat mesangial cell fibrotic phenotype: effect of gender.

Background And Aim: The protective role of angiotensin type 2 receptors (AT2-Rs) is still controversial. As AT2-Rs are minimally expressed in adult tissues the aim of the current study was to over-express AT2-Rs in rat mesangial cells in order to ascertain their potential role in modulating renal scarring.

Methods: Male and female mesangial cells were transiently transfected with AT2-R or control vector then 'injured' with macrophage-conditioned medium (MCM).

Atorvastatin improving renal ischemia reperfusion injury via direct inhibition of active caspase-3 in rats.

Caspase-3 is a key molecule involved in the inflammation and apoptosis of ischemia reperfusion (IR) injury. Statins are known to inhibit IR injury, but the mechanism of action remains uncertain. In the present study, the effect and underlying mechanism of ischemia alone, and reperfusion with or without atorvastatin (AT) as a timed intervention were examined, since clinically the kidney is only exposed to drug delivery during reperfusion.

Rat mesangial cells exhibit sex-specific profibrotic and proinflammatory phenotypes.

Background: Chronic renal disease progresses more rapidly in males compared to females. This study investigated whether there were any inherent differences between male and female mesangial cells that could contribute to this phenomenon and whether these differences could be modulated by sex hormones.

Methods: Experiments were carried out on cultured mesangial cells derived from adult male and female Wistar rat kidneys.

Perindoprilat modulates the activity of lipoprotein receptor-related protein in human mesangial cells.

Low density lipoprotein receptor-related protein (LRP) is a multifunctional endocytic receptor implicated in the modulation of a number of cellular processes, including the turnover of proteases and the degradation of extracellular matrix proteins. As such, it can play a key role in the control of fibrosis. The aim of this investigation was to ascertain whether the anti-fibrotic effects exerted by the angiotensin-converting enzyme inhibitor (ACE-I) perindoprilat on macrophage-conditioned medium (MPCM)-injured human mesangial cells can be modulated by this receptor.

Kallikrein gene 'knock-down' by small interfering RNA transfection induces a profibrotic phenotype in rat mesangial cells.

Background: Emerging evidence suggests that kallikrein exerts renoprotective effects independent of its haemodynamic actions. The aim of the current investigation was to delineate the role of kallikrein in the regulation of fibrosis, by 'knocking down' its expression using specific small interfering RNAs (siRNA).

Methods: Rat mesangial cells were treated with 12, 60, 120 nmol/l kallikrein-specific siRNAs.

Caspase-7, Fas and FasL in long-term renal ischaemia/reperfusion and immunosuppressive injuries in rats.

Background/aims: Ischaemia/reperfusion (I/R) injury is important in kidney transplantation. We have previously demonstrated that long-term I/R injury and immunosuppression affect apoptosis and inflammation, but the underlying mechanisms are far from clear. In this study, the involvement of caspase-7, Fas and FasL was further investigated.

Pharmacological enhancement of the kallikrein-kinin system promotes anti-fibrotic responses in human mesangial cells.

The aim of the present study was to investigate whether pharmacological enhancement of the renal kallikrein-kinin system using the vasopeptidase inhibitor omapatrilat plays a direct role in modulating the fibrotic responses of human mesangial cells to injury. Treatment with 40 micromol/L omapatrilat was able to reduce macrophage-conditioned medium (MPCM)-induced fibronectin levels without affecting mRNA expression. MPCM injury also suppressed kallikrein and low molecular weight kininogen mRNA.

The role of the alpha-1 adrenoceptor in modulating human mesangial cell matrix production.

Background: The sympathetic nervous system is frequently activated in hypertension and may modify various aspects of renal function. Whether modulation of the sympathetic nervous system directly influences the development of renal fibrosis is yet to be established. The current study investigates the role of the alpha-1 adrenoceptor on human mesangial cell scarring.

Diagnosis and monitoring a case of light-chain deposition disease in the kidney using a new, sensitive immunoassay.

A 59-year-old male was diagnosed with nephrotic syndrome secondary to light-chain deposition disease. There was no other evidence of a B cell clonal disorder or amyloidosis; circulating free light chains were identified using a new immunoassay (Freelite) and used to monitor disease progression. Improvement in renal function and proteinuria following VAMP chemotherapy correlated with a reduction in circulating light-chain levels.

The role of bradykinin in the antifibrotic actions of perindoprilat on human mesangial cells.

Background: Angiotensin-converting enzyme inhibitors (ACE-I) protect against the development of glomerulosclerosis using mechanisms partly dissociated from their systemic antihypertensive action. The aim of the current study was to delineate the mechanism of action underlying the antifibrotic effects of the ACE-I perindoprilat in the context of macrophage-mediated scarring in human mesangial cells.

Methods: Mesangial cells were treated with macrophage-conditioned medium (MPCM) in the presence or absence of the ACE-I perindoprilat.

Macrophage-induced rat mesangial cell expression of the 24p3-like protein alpha-2-microglobulin-related protein.

During screening of a murine macrophage cDNA repertoire for factors potentially able to modulate glomerular cell responses to injury, we identified a gene coding for the murine protein 24p3 lipocalin. Immunostaining of normal rat kidney sections showed positive 24p3-like staining in distal tubules/collecting ducts and small muscular arteries. Although most glomeruli were negative, some did exhibit small numbers of positively stained cells.

Fatty acids carried on albumin modulate proximal tubular cell fibronectin production: a role for protein kinase C.

Background: Proteinuric renal disease is associated with accumulation of tubulointerstitial matrix proteins. Human proximal tubular cells (PTCs) produce fibronectin in response to serum proteins but not albumin alone. It has been suggested that renal toxicity of filtered albumin depends on its lipid moiety.

Fatty acids exacerbate tubulointerstitial injury in protein-overload proteinuria.

The role of the albumin-carried fatty acids in the induction of tubulointerstitial injury was studied in protein-overload proteinuria. Rats were injected with fatty acid-carrying BSA [FA(+)BSA], fatty acid-depleted BSA [FA(-)BSA], or saline. Macrophage infiltration was measured by immunohistochemical staining, apoptotic cells were detected by in situ end labeling, and proliferating cells were identified by in situ hybridization for histone mRNA.

A placebo-controlled trial examining atorvastatin in dyslipidemic patients undergoing CAPD.

Background: Individuals with chronic renal disease are at high risk of cardiovascular morbidity and mortality, and therefore the management of dyslipidemia is particularly important in this patient population. This double-blind randomized study investigated the efficacy and safety of the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, atorvastatin, in continuous ambulatory peritoneal dialysis (CAPD) patients with dyslipidemia.

Methods: Following a two- to four-week baseline period, patients with low-density lipoprotein (LDL)-cholesterol > or =3.