No abstract

The R5 subfamily of receptor-type protein tyrosine phosphatases (RPTPs) comprises PTPRZ and PTPRG. A recent study on primary human glioblastomas suggested a close association between PTPRZ1 (human PTPRZ) expression and cancer stemness. However, the functional roles of PTPRZ activity in glioma stem cells have remained unclear. In the present study, we found that sphere-forming cells from the rat C6 and human U251 glioblastoma cell lines showed high expression levels of PTPRZ-B, the short receptor isoform of PTPRZ. Stable PTPRZ knockdown altered the expression levels of stem cell transcription factors such as SOX2, OLIG2, and POU3F2 and decreased the sphere-forming abilities of these cells. Suppressive effects on the cancer stem-like properties of the cells were also observed following the knockdown of PTPRG. Here, we identified NAZ2329, a cell-permeable small molecule that allosterically inhibits both PTPRZ and PTPRG. NAZ2329 reduced the expression of SOX2 in C6 and U251 cells and abrogated the sphere-forming abilities of these cells. Tumor growth in the C6 xenograft mouse model was significantly slower with the co-treatment of NAZ2329 with temozolomide, an alkylating agent, than with the individual treatments. These results indicate that pharmacological inhibition of R5 RPTPs is a promising strategy for the treatment of malignant gliomas.

Mesenchymal stem cells (MSCs) possess the capacity for site-specific differentiation of cell types in response to cues provided by different organs. This phenomenon suggests that MSCs participate in cutaneous wound regeneration. However, there are no prior reports on the influence of the local application of MSCs on cutaneous wound regeneration. To examine the effects of MSCs on wound regeneration, we cultured bone marrow cells of the femur of rats and treated the plastic adherent cells with a differentiation medium to induce differentiation. After treatment, we found that the bone marrow-derived plastic adherent cells possessed myogenesis, chondrogenesis, and adipogenesis capabilities, indicating that these cells are MSCs. The bone marrow-derived plastic adherent cells were injected intradermally into the skin of rats, and linear full-thickness incisional wounds were made immediately through the injected area. At 14 days after operation, wounds transplanted with bone marrow-derived plastic adherent cells had healed with very fine scars. Collagen architecture was thick and appeared to be similar to normal dermis. Histomorphologic scale analysis demonstrated significant differences between the control and the wounds transplanted with bone marrowderived plastic adherent cells. These results indicate that transplanted MSCs can respond quite normally to wound healing and regenerate dermal structure.

No abstract

Ghrelin was recently isolated from the rat stomach as an endogenous ligand for the GH secretagogue receptor. Although it is well known that a large amount of ghrelin is produced in the gastrointestinal tract, developmental changes in ghrelin mRNA expression and differentiation of ghrelin-immunopositive (ghrelin-ip) and mRNAexpressing (ghrelin-ex) cells in the stomach have not been elucidated.In this study, we therefore investigated the changes in ghrelin mRNA expression levels and in the numbers of ghrelin-ip and -ex cells in the stomachs of 1-to 8-week-old male and female rats by Northern blot analysis, immunohistochemistry and in situ hybridization. Northern blot analysis showed that the level of weak ghrelin mRNA expression was low in the postnatal period but then increased in a dimorphic pattern, i.e. transient stagnation at 4 weeks in the male rats and at 5 weeks in the female rats. The number of ghrelin-ip and ghrelin-ex cells also increased after birth, and more numerous ghrelin cells were found in female rats than in male rats, and this finding was confirmed by Northern blot analysis. Ghrelin-ip and -ex cells first appeared in the glandular base of the fundic gland and then they were found in the glandular base and the glandular neck at 3 weeks of age, suggesting that the distribution of ghrelin cells is extended from the glandular base to the glandular neck during the postneonatal development period. This is the first report on detailed changes in postneonatal ghrelin expression level and in the number of ghrelin cells in the rat stomach. The sexual dimorphism of ghrelin expression and ghrelin cell differentiation suggest that ghrelin plays an important physiological role in the stomach.