While the glomerular number was not different between these two groups of mice, the diabetic SA/- mice had significantly less proteinuria, mesangial expansion, glomerular cell proliferation, and macrophage infiltration than the diabetic SA/+ mice. The reduction in
Stat3 activity did selleck screening library not affect glomerular hyperfiltration seen after the induction of diabetes, as it was increased to the same degree in both groups of mice. Phosphorylation of Stat3 was markedly increased in the glomeruli of diabetic SA/+ mice compared to diabetic SA/- mice. The expression of inflammatory markers, IL-6, MCP-1, and activated NF-kappa B; type IV collagen, TGF-beta, and ICAM-1 mRNA; or type IV collagen and TGF-beta protein, were all found to be significantly less in glomeruli isolated from diabetic SA/- mice, as compared with diabetic SA/+ mice. Our study shows that Stat3 plays a critical role in the regulation of inflammation and abnormal matrix synthesis at an early stage of DN.”
“Purpose: “”Naked”" human mesenchymal stem cells (MSC)are neuro-protective in experimental brain injury (TBI). In a controlled
cortical impact (CCI) rat model, we investigated whether buy LCL161 encapsulated MSC (eMSC) act similarly, and whether efficacy is augmented using cells transfected to produce the neuro-protective substance glucagon-like peptide-1 (GLP-1). Methods: Thirty two Sprague-Dawley rats were randomized to five groups: controls (no CCI), CCI-only, CCI + eMSC, CCI + GLP-1 eMSC, and CCI + empty capsules. On day 14, cisternal cerebro-spinal fluid (CSF) was sampled for measurement of GLP-1 concentration. Brains were immuno-histochemically assessed using specific antibody staining for NeuN, MAP-2 and GFAR In another nine healthy rats, in vitro Results: GLP-1 production rates were measured from cells explanted after 2, 7 and 14 days. GLP-1 production rate in transfected cells, before implantation, was 7.03 fmol/capsule/h. Cells were still secreting GLP-1 at a rate of 3.68 +/- 0.49, 2.85 +/- 0.45 and 3.53 +/- 0.55 after 2, 7 and 14 days, respectively. In both
of the stem cell treated CCI groups, hippocampal cell loss was reduced, along with an attenuation of cortical neuronal and glial abnormalities, as measured by MAP-2 and GFAP expression. The effects Glutathione peroxidase were more pronounced in animals treated with GLP-1 secreting eMSC. This group displayed an increased CSF level of GLP-1 (17.3 +/- 3.4 pM). Conclusions: Hippocampal neuronal cell loss, and cortical glial and neuronal cyto-skeletal abnormalities, after CCI are reduced following transplantation of encapsulated eMSC. These effects were augmented by GLP-1 transfected eMSC. (C) 2009 Elsevier Ireland Ltd. All rights reserved.”
“Transforming growth factor-beta 1 (TGF-beta 1) is known to induce progression of experimental renal disease.