Int J Clin Exp Patho
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Int J Clin Exp Patho · Jan 2013
Expression of Wnt5a and its receptor Fzd2 is changed in the spinal cord of adult amyotrophic lateral sclerosis transgenic mice.
Wnt5a, a member of the Wnt gene family, encodes a cysteine-rich growth factor involved in signal transduction during growth and differentiation. The Fzd2 gene codes for a cell membrane receptor called Frizzled-2 have a structure similar to G protein coupled receptors. The extracellular N-terminal of the Fzd2 receptor has a cysteine-rich domain (CRD) that binds Wnt ligands and thus primes the Wnt signal pathway. ⋯ The influence of Wnt5a and Fzd2 signal transduction pathway on ALS was investigated in adult SOD1(G93A) transgenic mice. Changes in Wnt5a and Fzd2 expression in the spinal cord of SOD1(G93A) transgenic mice (ALS), SOD1(G93A) transfected NSC-34 cells, and primary cultures of astrocytes from SOD1(G93A) transgenic mice were detected by immunofluorescent staining, reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting. The results provide further insight into the role of Wnt5a and Fzd2 in the pathogenesis of ALS transgenic mice, which provides evidence that should help in the search for treatments of ALS.
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Int J Clin Exp Patho · Jan 2013
IL4 and IL-17A provide a Th2/Th17-polarized inflammatory milieu in favor of TGF-β1 to induce bronchial epithelial-mesenchymal transition (EMT).
Severe asthma is a chronic airway disease characterized by the Th2/Th17-polarized inflammation along with permanent airway remodeling. Despite past extensive studies, the exact role for Th2 and Th17 cytokines in asthmatic pathoetiology, particularly in the pathogenesis of bronchial epithelial-mesenchymal transition (EMT), is yet to be fully addressed. We herein conducted studies in 16-HBE cells and demonstrated that Th2-derived IL-4 and Th17-derived IL-17A provide a chronic inflammatory milieu that favors TGF-β1 to induce bronchial EMT. ⋯ IL-4 and IL-17A synergized with TGF-β1 to induce epithelial cells re-entering cell cycle, and to promote epithelial to mesenchymal morphological transistion, and by which they enhanced the capacity of TGF-β1 to suppress E-cadherin expression, and to induce a-SMA expression in epithelial cells. Mechanistic studies revealed that this synergic action is coordinated by the regulation of ERK1/2 activity. Our results not only provide a novel insight into the understanding of the mechanisms underlying airway remodeling in asthmatic condition, but also have the potential for developing more effective therapeutic strategies against severe asthmatics in clinical settings.
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Int J Clin Exp Patho · Jan 2013
Effects of glycyl-glutamine dipeptide supplementation on myocardial damage and cardiac function in rats after severe burn injury.
Glutamine decreases myocardial damage in ischemia/reperfusion injury. However, the cardioprotective effect of glutamine after burn injury remains unclear. Present study was to explore the protective effect of glycyl-glutamine dipeptide on myocardial damage in severe burn rats. ⋯ Compared with B group, the CK, LDH, AST and blood lactic acid levels reduced, myocardium ATP and GSH content increased in GG group. Moreover, the inhibition of cardiac contractile function and myocardial histopathological damage were reduced significantly in GG group. We conclude that myocardial histological structure and function were damaged significantly after burn injury, glycyl-glutamine dipeptide supplementation is beneficial to myocardial preservation by improving cardiocyte energy metabolism, increasing ATP and glutathione synthesis.
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Int J Clin Exp Patho · Jan 2013
Suppressing the malignant phenotypes of glioma cells by lentiviral delivery of small hairpin RNA targeting hypoxia-inducible factor-1α.
Hypoxic microenvironment of solid tumors is known to shape malignant phenotypes of cancer cells through the dimeric transcription factor hypoxia-inducible factor (HIF)-1. In the present study, the therapeutic effect of targeting α subunit of HIF-1 in glioma cells via lentiviral delivery of small hairpin RNA (shRNA) was evaluated. ⋯ Xenograft experiments in nude mice further showed that HIF-1α-shRNA inhibited tumor growth and caused persistent repression of HIF-1α and its target genes, including VEGF, GLUT1 and MMP2, up to 25 days post-inoculation. Taken together, lentiviral delivery of shRNA is a promising therapeutic approach for targeting HIF-1α in glioma.
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Int J Clin Exp Patho · Jan 2013
Comparative StudyFerritin L and Ferritin H are differentially located within hepatic and extra hepatic organs under physiological and acute phase conditions.
Ferritin L (FTL) and Ferritin H (FTH) subunits are responsible for intercellular iron storage. We previously reported increasing amounts of liver cytoplasmic and nuclear iron content during acute phase response (APR). Aim of the present study is to demonstrate intracellular localization of ferritin subunits in liver compared with extra hepatic organs of rat under physiological and acute phase conditions. ⋯ Similarly, in heart, spleen and brain FTL was detected mainly in the cytoplasm while FTH demonstrated intense nuclear and a weak cytoplasmic expression. Western blot analysis of cytoplasmic and nuclear fractions from liver, heart, spleen and brain further confirmed mainly cytoplasmic expression of FTL in contrast to the nuclear and cytoplasmic expression of FTH. The data presented demonstrate the differential localization of FTL and FTH within hepatic and extra hepatic organs being FTL predominantly in the cytoplasm while FTH predominantly in nucleus.