Urokinase plasminogen activator (uPA) belongs to a family of proteins that contains kringle domain and plays an important role in inflammation, tissue remodeling, angiogenesis, and tumor metastasis by pericellular plasminogen activation. Kringle domains of plasminogen have been shown to demonstrate anti-angiogenic and anti-tumor activities. Here, we report our investigation of the kringle domain of uPA for anti-angiogenic activity and a possible cellular mechanism of action. The recombinant kringle domain of uPA (Asp 45 -Lys 135 ) (UK1) inhibited endothelial cell proliferation stimulated by basic fibroblast growth factor, vascular endothelial growth factor (VEGF), or epidermal growth factor. It also inhibited migration of endothelial cells induced by VEGF or uPA, and in vivo angiogenesis on the chick chorioallantoic membrane. It did not block plasminogen activation by activated uPA in clot lysis and chromogenic substrate assays. Neither binding of UK1 to immobilized uPA receptor nor competitive inhibition of uPA binding were confirmed by real-time interaction analysis. However, internalization of UK1 followed by translocation from cytosol to nucleus was determined to be specific to endothelial cells. It also elicited a transient increase of Ca 2؉ flux of more than 2-fold within 2 min of exposure in an endothelial cell-specific manner. These results suggest that the kringle domain of uPA exhibits anti-angiogenic activity and that its anti-angiogenic activity may occur through a different mechanism from inhibition of uPA-uPA receptor interaction or uPA proteolytic activity and may be associated with endothelialcell specific internalization not mediated by the uPA receptor.

TUDCA promote the chondrogenic properties of osteoarthritic chondrocytes at submicellar concentrations by reducing the intracellular cholesterol and increasing membrane fluidity.

Microalbuminuria is an indicator of renal disease and is known to be related to obesity. The aim of this study is to investigate the association between the cross-sectional area of visceral adipose tissue (VAT) and the prevalence of microalbuminuria. We conducted a cross-sectional study of 1154 subjects who underwent routine checkups, including computed tomography (CT) scans of abdominal adipose tissue. We used the lowest tertile as a reference of abdominal fat. The highest tertile of VAT was related to the highest prevalence of microalbuminuria (odds ratio (OR): 1.96; 95% CI: 1.12-3.43). Subcutaneous adipose tissue (SAT) was not associated with microalbuminuria. In men, the highest tertile for VAT was associated with the highest prevalence of microalbuminuria (OR: 2.74; 95% CI: 1.44-5.22). In women, VAT or SAT was not associated with microalbuminuria. In nondiabetic subjects, the highest tertile for VAT was associated with the highest prevalence of microalbuminuria (OR: 2.23; 95% CI: 1.15-4.32). Among subjects without metabolic syndrome or with body mass index <25 kg m(-2), the highest tertile for VAT was associated with microalbuminuria in age- and sex-adjusted model, respectively (OR: 1.62; 95% CI: 1.01-2.31; OR: 2.21; 95% CI: 1.05-4.65). The analysis of the association of VAT and insulin resistance (IR) indicated that a higher VAT was associated with a higher IR (highest tertile for VAT-OR: 2.91; 95% CI: 1.70-4.96). In conclusion, the highest VAT of the current study was significantly correlated with the highest prevalence of microalbuminuria, even in traditionally low-risk subjects without diabetes, and this association is potentially related with a higher IR.

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