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Urate is produced as the major end product of purine metabolism. In the last decade, the incidence of hyperuricemia increased markedly, and similar trends in the epidemiology of metabolic syndrome have been observed. Hyperuficemia is associated with renal disease, and recent studies have reported that mild hyperuricemia results in hypertension, intrarenal vascular disease, and renal injury. This has led to the hypothesis that uric acid may contribute to renal fibrosis and progressive renal disease. Our purpose was to investigate the relationship between uric acid and renal tubular injury. We applied the method of intraperitoneal injection of uric acid to generate the hyperuricemic mouse model. Compared with the saline injection group, the expression of lysyl oxidase (LOX) and fibronectin in kidneys was increased significantly in hyperuricemic groups. In vitro, uric acid significantly induced NRK-52E cells to express the ECM marker fibronectin, as well as LOX, which plays a pivotal role in ECM maturation, in a time- and dose-dependent manner. Upregulation of the urate transporter URATI, which is located in the apical membrane of proximal tubules, sensitized the uric acid-induced fibronectin and LOX induction, while both knocking down URAT1 expression in tubular epithelial cells by RNA interference and inhibiting URAT1 function pharmacologically attenuated LOX and fibronectin expression. Furthermore, knockdown of LOX expression by a small interfering RNA strategy led to a decrease in fibronectin abundance induced by uric acid treatment. In addition, evidence of a uric acid-induced activation of the NF-[kappa]B signaling cascade was observed. Our findings highlight a need for carefully reevaluating our previous view on the pathological roles of hyperuricemia in the kidney and nephropathy induced by uric acid in clinical practice. NF-[kappa]B doi: 10.1152/ajprenal.00053.2010.

A dimeric 140 kDa [(Fib-2).sub.2] fragment containing both Fib-2 regions are prepared by limited proteolysis in order to clarify the role of another pair of fibrin-binding regions, Fib-2, located at the disulfide-linked COOH-terminal ends of fibronectin. Experiments revealed about 30% inhibition of the Fib-2 mediated binding by increasing concentrations of Fib-1 fragment.

Adsorption and desorption of fibronectin (FN) were investigated at thin films of alternating maleic acid copolymers with octadecene (POMA) and with propene (PPMA). The results reveal that the interfacial mode of adsorbed FN depends on the predominant interactions and large amounts of FN were tightly bound to POMA by hydrophobic interactions whereas FN adsorbed on PPMA was concluded to attain an unfolded structure allowing for the electrostatic matching of positively charged residues on FN with the maleic acid groups.

Cells rapidly transduce forces exerted on extracellular matrix contacts into tyrosine kinase activation and recruitment of cytoskeletal proteins to reinforce integrincytoskeleton connections and initiate adhesion site formation. The relationship between these two processes has not been defined, particularly at the submicrometer level. Using talin1-deficient cells, it appears that talin1 is critical for building early mechanical linkages. Deletion of talin1 blocked laser tweezers, force-dependent reinforcement of submicrometer fibronectin-coated beads and early formation of adhesion sites in response to force, even though Src family kinases, focal adhesion kinase, and spreading were activated normally. Recruitment of vinculin and paxillin to sites of force application also required talin1. FilaminA had a secondary role in strengthening fibronectin--integrin--cytoskeleton connections and no role in stretch-dependent adhesion site assembly. Thus, force-dependent activation of tyrosine kinases is independent of early force-dependent structural changes that require talin1 as part of a critical scaffold.

The time-resolved fluorescence anisotropy technique is employed to explain the interaction taking place between the bovine fibronectin type II (Fn2) protein PDC-109 and cholesterol. The rotational mobility of the cholesterol is shown to be highly reduced by the presence of the protein.

A study on relationships between the effect of angiogenin, a major angiogenic factor and extracellular nitric oxide (NO) release, a well known biological mediator involved in vascular physiology is presented. The results provide insight into the mechanism leading to NO production and the interaction of angiogenin with the cell nucleus to activate nitric oxide synthase (NOS).

The analysis helps in the identification of a gene, which can be used for the encoding of a modular xylase from Cellulosimicrobium sp. strain HY-13. The various different functional domains present in the xylase are also discussed.

The internalization ability of Lactococcus lactis internalin A (InI[A.sup.+]) and Lactococcus lactis producing either the fibronectin-binding protein A of Staphylococcus aureus (L. lactis FbBP[A.sup.+]) or its fibronectin binding domains C and D (L. lactis C[D.sup.+]) is compared. L. lactis FnBP[A.sup.+] and L. lactis FnBP[A.sup.+] has displayed comparable internalization rates in Caco-2 cells, while the internalization rate seen with L. lactis C[D.sup.+] is lower.

A study related to the interaction between anastellin and the third fibronectic (FN) type III domain (III3), which is a key anastellin binding site on FN is reported. The findings from the matrix-assisted laser desorption ionization-time-of-flight (MALDI-TOF) mass spectrometry indicated that the middle part of III3 became destabilized and protease sensitive upon anastellin binding and hence the stability of III3 appears to be a key factor in anastellin binding.

The development of a mutlivalent strategy by fusing an [[alpha].sub.v][[beta].sub.3]-binding fibronectin type III (FN3) monobody with a short cartilage oligomeric matrix protein pentamerization domain is reported. The FN3 monobody binds to the tumor-related biomarkers with exceptional high strength and stability.