Using quantitative real-time polymerase chain reaction and parallel analysis of a carefully selected group of reference genes, we have determined the relative expression of each PDE isoenzyme across the 24 selected tissues, and also compared the expression of selected PDEs to each other within a given tissue type. Several PDEs show strikingly selective expression (e.g. PDE10A and PDE1B mRNA levels in the caudate nucleus are 20-fold higher than in most other tissues; PDE1C and PDE3A are highly expressed in the heart and PDE8B is expressed very strongly in the thyroid gland). This comprehensive approach provides a coherent and
quantitative view of the mRNA expression of the PDE gene family and enables an integration of data obtained with other non-quantitative methods. (C) 2010 Published by Elsevier Ltd.”
“Hepatocyte growth factor (HGF) is a potent antifibrotic protein that inhibits kidney fibrosis through several mechanisms. selleck To study its role in podocyte homeostasis, injury, and repair in vivo, we generated conditional knockout Quizartinib research buy mice in which the HGF receptor, c-met, was specifically deleted in podocytes using the Cre-LoxP system. Mice with podocyte-specific ablation of c-met (podo-met(-/-)) developed normally. No albuminuria or overt pathologic lesions were detected up
to 6 months of age, suggesting that HGF signaling is dispensable for podocyte maturation, survival, and function under normal physiologic conditions. However, after adriamycin treatment, podo-met(-/-) mice developed more severe podocyte injury and albuminuria than their control littermates. Ablation of c-met also resulted in more profound suppression of Wilms tumor 1 (WT1) and nephrin expression, and podocyte apoptosis after injury. When HGF was expressed ectopically in vivo, it ameliorated adriamycin-induced albuminuria, preserved WT1 and nephrin expression, and inhibited podocyte apoptosis. However, exogenous
HGF failed to significantly reduce albuminuria in podo-met(-/-) mice, suggesting that podocyte-specific c-met TEW-7197 manufacturer activation by HGF confers renal protection. In vitro, HGF was able to preserve WT1 and nephrin expression in cultured podocytes after adriamycin treatment. HGF also protected podocytes from apoptosis induced by a lethal dose of adriamycin primarily through a phosphoinositide 3-kinase (PI3K)/Akt-dependent pathway. Collectively, these results indicate that HGF/c-met signaling has an important role in protecting podocytes from injury, thereby reducing proteinuria. Kidney International (2010) 77, 962-973; doi:10.1038/ki.2010.40; published online 10 March 2010″
“Agomelatine, a novel melatonin analogue and anti-depressant that acts as an agonist on melatonin receptors 1 and 2 and as an antagonist at the 5HT2C receptor, was tested for its effects on cell proliferation in the dentate gyrus of the adult rat hippocampus under intact and flattened corticosterone rhythm conditions.