reparative role of CD34[+] cells in human nephropathies

Stem cells are defined by the two properties of self renewal and pleuripotency. In different adult tissues, they generate new cells either continuously or in response to injury depending on local factors in the surrounding microenvironment which direct their line of differentiation. Circulating stem cells frequently engraft into the kidney and differentiate into renal parenchymal cells [tubular epithelial cells, podocytes, mesangial cells and fib roast]. This study included 36 human renal biopsies of different types of glomerulonephritis to determine the role of stem cells in the repair process of glomerulonephritis. Renal biopsies were stained immunohistochemically with monoclonal anti - CD34 antibodies, the stem cell marker as well as alpha SMA, Vimentin, Proliferating Cell Nuclear Antigen [PCNA], Insitu End Labeling [ISEL], CD68. Positivity was evaluated using a point counting technique in the glomeruli and by counting individual positive cells per HPF [X400] in the interstitium. To rule out the endothelial nature of positive cells, double staining for factor IIX related antigen and CD31 was done. CD34 positive cells were detected in the glomerular mesangial areas with peripheral accentuation suggestive of a visceral epithelial distribution, tubular epithelial cells [cytoplasmic in 3/36 cases and in the luminal border of the rest of the cases] as well as in isolated cells in the renal interstitium, these cells also double stained for alpha SMA. CD34 positivity was counted in the glomeruli [3.05 +/- 0.58], tubules [6.38 +/- 2.58] and for interstitial areas [9.76 +/- 2.34]. Significant positive correlation between glomerular CD34 and glomerular regeneration ratio was found. These results imply the presence and may be a role for stem cells in the repair process of glomerulonephritis

Heat shock protein 27 interacts with vimentin and prevents insolubilization of vimentin subunits induced by cadmium

Vimentin is an intermediate filament that regulates cell attachment and subcellular organization. In this study, vimentin filaments were morphologically altered, and its soluble subunits were rapidly reduced via cadmium chloride treatment. Cadmium chloride stimulated three major mitogen-activated protein kinases (MAPKs): extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38, and led apoptotic pathway via caspase-9 and caspase-3 activations. In order to determine whether MAPKs were involved in this cadmium-induced soluble vimentin disappearance, we applied MAPK- specific inhibitors (PD98059, SP600125, SB203580). These inhibitors did not abolish the cadmium-induced soluble vimentin disappearance. Caspase and proteosome degradation pathway were also not involved in soluble vimentin disappearance. When we observed vimentin levels in soluble and insoluble fractions, soluble vimentin subunits shifted to an insoluble fraction. As we discovered that heat- shock protein 27 (HSP27) was colocalized and physically associated with vimentin in unstressed cells, the roles of HSP27 with regard to vimentin were assessed. HSP27-overexpressing cells prevented morphological alterations of the vimentin filaments, as well as reductions of soluble vimentin, in the cadmium-treated cells. Moreover, HSP27 antisense oligonucleotide augmented these cadmium-induced changes in vimentin. These findings indicate that HSP27 prevents disruption of the vimentin intermediate filament networks and soluble vimentin disappearance, by virtue of its physical interaction with vimentin in cadmium-treated SK-N-SH cells.