ABSTRACT
BACKGROUND:Results of recent studies demonstrated the modulation of thymosin β4 on hair cycle and regeneration, but the mechanism of action remains unclear. OBJECTIVE:To investigate the mechanism by which thymosinβ4 increases hair regeneration through Wnt signal pathway. METHODS:After the mouse model of depilation was established using rosin/paraffin mixed agents, the experimental animals were randomly assorted to three different groups, including low-dose, high-dose and control groups, and a dose of 0.3μg/50μL, 3μg/50μL thymosinβ4 and PBS was administered on the depilated backs every 12 hours, respectively. Then photography, hematoxylin-eosin staining, immunohistochemistry and in situ hybridization were applied to observe the growth of hair, and the expressions ofβ-catenin and LEF-1 mRNA in different groups at different time were quantitatively evaluated. RESULTS AND CONCLUSION:The hair growth of the low-dose group was faster than that of the other groups. Hematoxylin-eosin staining demonstrated inflammatory cel s infiltration in the dermis after depilation, and the number of hair fol icles that were in the phase of anagen was much more than the other groups as time went by. Immunohistochemistry ofβ-catenin showed the accumulation of intra-cel ularβ-catenin in the low-dose group at the bulge of fol icles assessed by integrated absorbance analysis (P<0.05), so did the in situ hybridization of LEF-1 mRNA. Low-dose thymosinβ4 accelerates hair growth through Wnt signal pathway by elevating the level ofβ-catenin and LEF-1 mRNA.
ABSTRACT
Bone marrow mesenchymal stem cells (MSCs) are considered as a promising cell source to treat the acute myocardial infarction. However, over 90% of the stem cells usually die in the first three days of transplantation. Survival potential, migration ability and paracrine capacity have been considered as the most important three factors for cell transplantation in the ischemic cardiac treatment. We hypothesized that stromal-derived factor-1 (SDF-1)/CXCR4 axis plays a critical role in the regulation of these processes. In this study, apoptosis was induced by exposure of MSCs to H(2)O(2) for 2 h. After re-oxygenation, the SDF-1 pretreated MSCs demonstrated a significant increase in survival and proliferation. SDF-1 pretreatment also enhanced the migration and increased the secretion of pro-survival and angiogenic cytokines including basic fibroblast growth factor and vascular endothelial growth factor. Western blot and RT-PCR demonstrated that SDF-1 pretreatment significantly activated the pro-survival Akt and Erk signaling pathways and up-regulated Bcl-2/Bax ratio. These protective effects were partially inhibited by AMD3100, an antagonist of CXCR4.We conclude that the SDF-1/CXCR4 axis is critical for MSC survival, migration and cytokine secretion.
Subject(s)
Animals , Male , Rats , Apoptosis , Apoptosis Regulatory Proteins , Genetics , Metabolism , Bone Marrow Cells , Metabolism , Physiology , Cell Hypoxia , Cell Movement , Chemokine CXCL12 , Genetics , Pharmacology , Physiology , Cytokines , Metabolism , Gene Expression , L-Lactate Dehydrogenase , Metabolism , MAP Kinase Signaling System , Mesenchymal Stem Cells , Metabolism , Physiology , Proto-Oncogene Proteins c-akt , Metabolism , Rats, Sprague-Dawley , Receptors, CXCR4 , MetabolismABSTRACT
The alphaB-crystallin, which is a member of small heat shock protein (sHSP), was initially identified as a component of a vertebrate eye lens protein, and also shown to be expressed in non-lenticular tissues including cardiac muscles and the central nervous system. Recently, it was demonstrated that alphaB-crystallin expression was increased in the brain of patients suffering various neurological diseases including Alzheimers disease. In the current study, we examined in detail the time-course of alphaB-crystallin expression in the region of neuronal loss and in activated glia cells in hippocampus of the KA-treated mouse brain. The alphaB-crystallin was expressed in pyramidal layer and in oligodendrocytes of hippocampus 1 day after KA-treatment, which was similar to that in normal mice. The alphaB-crystallin expression began to be increased 2 days after KA-treatment and reached peak induction, especially in astrocytes in the CA3 area of hippocampus 4 days after KA-treatment. Immunofluorescent staining with anti-alphaB-crystallin and anti-GFAP antibodies revealed that the induction of alphaB-crystallin was localized in the activated astrocytes, prominently in the CA3 region of hippocampus where a severe neuronal death was undergoing. The results suggested that alphaB-crystallin might play a role in reactive gliosis and/or in delayed neuronal death proceeded in KA-induced epileptic brain.