ABSTRACT
Objective To explore the effect of Wntless ( Wls)-mediated Wnt signaling on the development and energy metabolism of brown adipose tissue (BAT). Methods BAT-specific Wls knockout (WlsMyf5Δ/Δ) mice were generated by Cre-loxP system. The differentiations of BAT in WlsMyf5Δ/Δ knockout mice and Wlsfl/fl control mice were analyzed by histological morphology, immunohistochemistry, real-time PCR, and Western blot. After stromal vascular fraction (SVF) cells in BAT were induced to differentiate, oil red O staining, real-time PCR, and cell respiration experiments were performed for analyzing in-vitro cell differentiation and oxygen consumption. The energy metabolism of mice was monitored by rectal temperature, oxygen consumption rate in BAT, and energy expenditure. The adiposity of mice was evaluated by NMR while the glucose metabolism was analyzed by the glucose and insulin tolerance tests. Results The WlsMyf5Δ/Δ knockout mice appeared smaller body size, lower weight, higher percentage of lean fat, lower size of BAT, with higher body temperature on the back as compared to Wlsfl/fl control mice. The differentiation and thermogenesis of BAT in Wls-deficient mice were relatively augmented, along with an increase in Ucp1 mRNA and protein expressions. SVF cells from BAT in WlsMyf5Δ/Δ knockout mice revealed enhanced brown differentiation. Adiposity was decreased and glucose metabolic capacity was enhanced in the WlsMyf5Δ/Δknockout mice, without significant change in the whole body. Conclusion Wls-mediated Wnt signaling decreases the thermogenesis and glucose metabolism of BAT by suppressing its differentiation.
ABSTRACT
Objective To explore the expression of Wnt secret protein Wntless in gastric carcinoma and normal mu-cosa,and to analyze the clinical significance of Wntless expression. Methods To detecte the expression of Wntless protein in gastric adenocarcinoma and normal gastric mucosa by immunohistochemistry. Results In 104 specimens of gastric cancer,the expression of Wntless in gastric adenocarcinoma was: 7.7% (8/104) cases were 0 or 1+, 36.5% (38/104) cases were 2+,and 55.8% (58/104) cases were 3+. While in normal mucosa,the expression of Wntless was:71.2% (74/104) cases were 0 or 1+, 19.2% (20/104) cases were 2+, and 9.6% (10/104) cases were 3+.The expression of Wntless in gastric adenocarcinoma was significantly higher than that in normal gas-tric mucosa (P<0.001). The expression of Wntless protein was positively correlated with tumor differentiation(P<0.05),and was positively correlated with lymph node metastasis (P<0.05).Conclusions Wntless is highly ex-pressed in gastric carcinomas and may have role in the oncogenesis. Wntless may be used as a new marker for pro-gression and metastasis of gastric carcinoma.
ABSTRACT
Objective To explore the expression of Wnt secret protein Wntless in gastric carcinoma and normal mu-cosa,and to analyze the clinical significance of Wntless expression. Methods To detecte the expression of Wntless protein in gastric adenocarcinoma and normal gastric mucosa by immunohistochemistry. Results In 104 specimens of gastric cancer,the expression of Wntless in gastric adenocarcinoma was: 7.7% (8/104) cases were 0 or 1+, 36.5% (38/104) cases were 2+,and 55.8% (58/104) cases were 3+. While in normal mucosa,the expression of Wntless was:71.2% (74/104) cases were 0 or 1+, 19.2% (20/104) cases were 2+, and 9.6% (10/104) cases were 3+.The expression of Wntless in gastric adenocarcinoma was significantly higher than that in normal gas-tric mucosa (P<0.001). The expression of Wntless protein was positively correlated with tumor differentiation(P<0.05),and was positively correlated with lymph node metastasis (P<0.05).Conclusions Wntless is highly ex-pressed in gastric carcinomas and may have role in the oncogenesis. Wntless may be used as a new marker for pro-gression and metastasis of gastric carcinoma.
ABSTRACT
PURPOSE: Wnt signaling plays an essential role in the dental epithelium and mesenchyme during tooth morphogenesis. Deletion of the Wntless (Wls) gene in odontoblasts appears to reduce canonical Wnt activity, leading to inhibition of odontoblast maturation. However, it remains unclear if autonomous Wnt ligands are necessary for differentiation of dental pulp cells into odontoblast-like cells to induce reparative dentinogenesis, one of well-known feature of pulp repair to form tertiary dentin. MATERIALS AND METHODS: To analyze the autonomous role of Wls for differentiation of dental pulp cells into odontoblast-like cells, we used primary dental pulp cells from unerupted molars of Wls-floxed allele mouse after infection with adenovirus for Cre recombinase expression to knockout the floxed Wls gene or control GFP expression. The differentiation of dental pulp cells into odontoblast-like cells was analyzed by quantitative real-time polymerase chain reaction. RESULT: Proliferation rate was significantly decreased in dental pulp cells with Cre expression for Wls knockout. The expression levels of Osterix (Osx), runt-related transcription factor 2 (Runx2), and nuclear factor I-C (Nfic) were all significantly decreased by 0.3-fold, 0.2-fold, and 0.3-fold respectively in dental pulp cells with Wls knockout. In addition, the expression levels of Bsp, Col1a1, Opn, and Alpl were significantly decreased by 0.7-fold, 0.3-fold, 0.8-fold, and 0.6-fold respectively in dental pulp cells with Wls knockout. CONCLUSION: Wnt ligands produced autonomously are necessary for proper proliferation and odontoblastic differentiation of mouse dental pulp cells toward further tertiary dentinogenesis.