The beneficial effect of DEXA on the TGF-beta 1-induced EMT was mediated through the amelioration of ERK

and p38 mitogen-activated protein kinase (MAPK) phosphorylation; however, this effect was not related to the TGF-beta 1-induced activation of Smad2/3 signaling. DEXA inhibited glycogen synthase kinase-3 beta (GSK-3 beta) phosphorylation www.selleckchem.com/products/azd5153.html and the Snail upregulation induced by TGF-beta 1, which were also ameliorated by inhibitors of MAPK. In conclusion, this is the first study demonstrating the protective effect of DEXA on the EMT in TGF-beta 1-stimulated HPMCs by inhibiting MAPK activation, GSK-3 beta phosphorylation and Snail upregulation. Laboratory Investigation (2013) 93, 194-206; doi:10.1038/labinvest.2012.166; published online 3 December 2012″
“Stress causes activation of the hypothalamic-pituitary-adrenal (HPA) axis, resulting in secretion learn more of corticosteroids which facilitate behavioural adaptation. These effects exerted by corticosteroids are mediated by two brain corticosteroid receptor types, the mineralocorticoid receptor (MR), with a high affinity already occupied under basal conditions and the glucocorticoid receptor (GR), with a low affinity only activated during stress.

Here, we studied MR gene haplotypes constituted by the two single nucleotide polymorphisms MR-2G/C (rs2070951) and MRI180V (rs5522). The haplotypes showed differences

in cortisol-induced gene transcription and protein expression while RAD001 the structural variant MRI180V did not affect ligand binding.

Moreover, in a well characterized cohort of 166 school teachers these haplotypes have been associated with perceived chronic

stress (Trier Inventory for the Assessment of Chronic Stress, TICS) and, in a subgroup of 47 subjects, with ACTH, cortisol and heart rate responses to acute psychosocial stress (Trier Social Stress Test, TSST). MR haplotypes were significantly associated with the TICS scales “”excessive demands at work”" and “”social overload”". Subjects homozygous for haplotype MR-2C/MRI180, which in vitro showed highest expression and transactivational activity, displayed the highest salivary cortisol (p < 0.001), plasma cortisol (p = 0.010), plasma ACTH (p = 0.003) and heart rate (p = 0.018) responses.

It is concluded that the investigated MR haplotypes modulate cortisol-induced gene transcription in vitro. Moreover, these haplotypes may contribute to individual differences in perceived chronic stress as well as neuroendocrine and cardiovascular stress responses. (c) 2010 Elsevier Ltd. All rights reserved.”
“We investigated the effects of loss of tenascin C on the healing of the stroma using incision-injured mice corneas. Tenascin C was upregulated in the stroma following incision injury to the cornea. Wild-type (WT) and tenascin C-null (knockout (KO)) mice on a C57BL/6 background were used.