ライフサイエンスコーパス: suPAR

1 suPAR also was increased in plasma from patients with EG

2 suPAR did not significantly stimulate cell signaling or

3 suPAR was measured by enzyme-linked immunosorbent assay,

4 suPAR was measured using a commercially available enzyme

5 suPAR-K139A/H143A displayed a 50% reduction in scuPA-med

6 tivation and causes proteinuria in mice in a suPAR-dependent manner.

7 0.6-44.2) to 39.3 (28.8-63.4; P<0.0001), and suPAR levels decreased from a median of 6.781 to 4.129 p

8 radation product, heat shock protein-70, and suPAR were measured in 3278 patients undergoing coronary

9 treatment of piglets with RAP, anti-LRP, and suPAR completely prevented, and the ERK MAPK antagonist

10 ta-2 microglobulin (beta-2 m), neopterin and suPAR soluble urokinase-type plasminogen activator recep

11 ormation of a zinc-dependent complex between suPAR and HKa.

12 dentified high-affinity interactions between suPAR, APOL1 and alphavbeta3 integrin, whereby APOL1 pro

13 We investigated the relationship between suPAR levels and podocyte changes and the impact of ther

14 The relationship between suPAR levels and the eGFR at baseline, the change in the

15 gonist of alphavbeta3 integrin RGDfv blocked suPAR-induced suppression of nephrin.

16 Circulating suPAR levels were elevated in 84.3% and 55.3% of patient

17 Here, we analyzed circulating suPAR levels in two cohorts of children and adults with

18 associations between a change in circulating suPAR with different therapeutic regimens and with remis

19 We show that circulating suPAR activates podocyte beta(3) integrin in both native

20 In conclusion, suPAR levels are elevated in geographically and ethnical

21 dance with the previous study, the delivered suPARs are deposited in the glomeruli.

22 EGFRvIII-expressing GBM cells, tumor-derived suPAR was detected in the plasma, and the level was sign

23 The cellular source(s) of elevated suPAR associated with future and progressing kidney dise

24 To determine whether elevated suPAR levels are associated with renal disease progressi

25 It is unknown whether elevated suPAR levels in patients with normal kidney function are

26 f 70 sessions of PE, which partly eliminated suPAR, with a mean reduction of 37 +/- 12% of serum conc

27 The synergy of circulating factor suPAR and APOL1 G1 or G2 on alphavbeta3 integrin activat

28 ants G1 and G2 exhibited higher affinity for suPAR-activated avb3 integrin than APOL1 G0.

29 lapping 20-amino acid peptides prepared from suPAR, two regions for HK binding were identified.

30 A high suPAR level >/=3.5 ng/mL was associated with all-cause d

31 ed an independent association between a high suPAR level at baseline and increased hazard rates for b

32 in the BM of proteinuric animals having high suPAR, and these cells efficiently transmit proteinuria

33 Patients with high suPAR levels were more likely to have progression of the

34 A higher suPAR level at baseline was associated with a greater de

35 , patients with an NPHS2 mutation had higher suPAR levels than those without a mutation.

36 suPAR, and strengthened in those with higher suPAR levels.

37 Together, these results identify suPAR as a functional connection between the BM and the

38 there was no sustained significant change in suPAR levels before and after the course of intensified

39 binding of scuPA to more than one epitope in suPAR is required for its optimal activation and associa

40 the gene encoding uPAR, forced increases in suPAR concentration result in FSGS-like glomerular lesio

41 In accordance with the results seen in suPAR-associated proteinuric animal models, in which kid

42 Binding of labeled suPAR/scuPA was inhibited by unlabeled complex, but not

43 e per 1.73 m(2)) at baseline had the largest suPAR-related decline in the eGFR.

44 the maximum activity induced by full-length suPAR (5 nM), respectively.

45 udy unveiled that interaction of full-length suPAR with alphavbeta3 integrin expressed on podocytes r

46 s phenomenon is mediated only by full-length suPAR, is time-and dose-dependent and is associated with

47 ple regression analysis suggested that lower suPAR levels associated with higher estimated GFR, male

48 d risk was attenuated in patients with lower suPAR, and strengthened in those with higher suPAR level

49 Biobank (mean age, 63 years; 65% men; median suPAR level, 3040 pg per milliliter) and determined rena

50 The activities of suPAR were replicated by conditioned medium (CM) from EG

51 Addition of suPAR to the 3-BRS significantly improved the C statisti

52 ct synergistically to inhibit the binding of suPAR and to stimulate plasminogen activator activity.

53 Binding of suPAR to alpha4beta1 and alphavbeta3 is blocked by known

54 scuPA induced the binding of suPAR to LM-TK- cells.

55 uPAR antibodies effectively block binding of suPAR to these integrins.

56 further find that a higher concentration of suPAR before transplantation underlies an increased risk

57 studies observed increased concentration of suPAR in various glomerular diseases and in other human

58 characterized by increased concentration of suPAR.

59 Further, little degradation of suPAR was detected, suggesting that cell-bound complex d

60 findings suggest that glomerular deposits of suPAR caused by elevated plasma levels are not sufficien

61 hree mouse models, we explore the effects of suPAR on kidney function and morphology.

62 However, such deposition of either form of suPAR in the kidney did not result in increased glomerul

63 model by demonstrating that the infusion of suPAR inhibits expression of nephrin and WT-1 in podocyt

64 An elevated level of suPAR was independently associated with incident chronic

65 ble for the elevated, pathological levels of suPAR, as evidenced by BM chimera and BM ablation and ce

66 However, whether overexpression of suPAR, per se, contributes to the pathogenesis of FSGS i

67 roceeded less efficiently in the presence of suPAR.

68 among participants in the lowest quartile of suPAR levels as compared with -4.2 ml per minute per 1.7

69 ic kidney disease in the highest quartile of suPAR levels was 3.13 times as high (95% confidence inte

70 ssociation between the relative reduction of suPAR after 26 weeks of treatment and reduction of prote

71 therapy results in significant reduction of suPAR levels and complete or significant improvement of

72 imens and with remission support the role of suPAR in the pathogenesis of FSGS.

73 ed by unlabeled complex, but not by scuPA or suPAR added separately, indicating cellular binding site

74 of plasma exchange (PE) on clinical outcome, suPAR levels, and in vitro podocyte beta3-integrin activ

75 (lo) cells in the BM, leading to high plasma suPAR and proteinuric kidney disease.

76 We measured plasma suPAR levels in 3683 persons enrolled in the Emory Cardi

77 rent FSGS and a temporary lowering of plasma suPAR as well as podocyte beta3-integrin activation.

78 APOL1 risk variants was dependent on plasma suPAR levels: APOL1-related risk was attenuated in patie

79 Median pretreatment suPAR levels were higher among those with severe (>/=75%

80 Purified suPAR was biologically active when added to cultures of

81 le urokinase plasminogen activator receptor (suPAR) and incident non-AIDS comorbidity and all-cause m

82 okinase-type plasminogen activator receptor (suPAR) are generally elevated in sera from children and

83 okinase-type plasminogen activator receptor (suPAR) as a circulating factor implicated in FSGS.

84 okinase-type plasminogen activator receptor (suPAR) have been associated with focal segmental glomeru

85 le urokinase plasminogen activator receptor (suPAR) independently predicts chronic kidney disease (CK

86 le urokinase plasminogen activator receptor (suPAR) is a circulating factor implicated in the onset a

87 okinase-type plasminogen activator receptor (suPAR) is implicated in the pathogenesis of native and r

88 asma soluble plasminogen activator receptor (suPAR) levels, which in turn induces chemotaxis of CD34

89 le urokinase plasminogen activator receptor (suPAR) prevents impairment of cerebrovasodilation induce

90 okinase-type plasminogen activator receptor (suPAR) was associated recently with focal segmental glom

91 okinase-type plasminogen activator receptor (suPAR) was performed with archived plasma samples to pre

92 le urokinase plasminogen activator receptor (suPAR), a marker of immune activation, is predictive of

93 le urokinase plasminogen activator receptor (suPAR), which contains the three domains of the wild-typ

94 le urokinase plasminogen activator receptor (suPAR).

95 and His(143) to alanine in soluble receptor (suPAR) reduced the affinity for scuPA approximately 5-fo

96 mposed of recombinant, soluble uPA receptor (suPAR) and single chain uPA (scuPA) to a cell line (LM-T

97 verexpression of soluble urokinase receptor (suPAR) causes pathology in animal models similar to prim

98 Recently, serum soluble urokinase receptor (suPAR) has been proposed as a cause of two thirds of cas

99 eport that serum soluble urokinase receptor (suPAR) is elevated in two-thirds of subjects with primar

100 Serum soluble urokinase receptor (suPAR) levels strongly predict incident CKD stage 3 in a

101 okinase-type plasminogen activator receptor, suPAR and neutrophil gelatinase-associated lipocalin, NG

102 and well characterized forms of recombinant suPAR produced by eukaryotic cells were administered ove

103 nded within 4 days concomitant with a rising suPAR level.

104 inhibited the enzymatic activity of WT-scuPA-suPAR unlike comparable concentrations of GFD.

105 Inhibition of scuPA/suPAR activity was evident at a Glu-plasminogen concentr

106 Inhibition of scuPA/suPAR by plasminogen was completely abolished in the pre

107 creased the Michaelis constant (Km) of scuPA/suPAR from 18 nM to 49 nM, and decreased the catalytic c

108 -3 inhibited the enzymatic activity of scuPA/suPAR with an inhibition constant (Ki) equal to 1.9 micr

109 plasminogen activator activity of the scuPA/suPAR complex is inhibited by Glu- and Lys-plasminogen,

110 by which the enzymatic activity of the scuPA/suPAR complex is regulated is only partially understood.

111 Serum suPAR level was measured at enrollment, and eGFR was mea

112 Serum suPAR was found to be elevated in all transplant candida

113 In advanced renal disease, elevated serum suPAR is not unique to FSGS cases.

114 Our study identifies serum suPAR as a circulating factor that may cause FSGS.

115 e disease can be abrogated by lowering serum suPAR concentrations through plasmapheresis, or by inter

116 study demonstrated elevated levels of serum suPAR in patients with the disease.

117 07) and the 4C Study (2010-2016), with serum suPAR level measured at enrollment and longitudinal eGFR

118 R is a low percentage binding event and that suPAR and full-length uPAR bind the Man-6-P/IGF2R by dif

119 Here, we show that suPAR induces nephrin down-modulation in human podocytes

120 These results suggest that suPAR may function as an important paracrine signaling f

121 Indeed, the suPAR-Man-6-P/IGF2R interaction was inhibited by Man-6-P

122 epresented a minor percentage (8-30%) of the suPAR present.

123 h plasmapheresis, or by interfering with the suPAR-beta(3) integrin interaction through antibodies an

124 Binding of PaI-1 to suPAR/scuPA complexes is totally reversible and can be o

125 utrophils demonstrated increased adhesion to suPAR, which was abrogated by blocking of low-density li

126 of D2 (Leu166-Thr195) blocked HK binding to suPAR and to human umbilical vein endothelial cells (HUV

127 ely inhibited biotin-HK or -46HKa binding to suPAR.

128 HK predominantly bound to suPAR fragments containing domains 2 and 3 (S-D2D3).

129 When scuPA bound to suPAR, a binding site for alpha 2-macroglobulin receptor

130 Binding of biotin-HK to suPAR was inhibited by HK, 56HKa, and 46HKa with an IC50

131 and urokinase inhibited the binding of HK to suPAR.

132 Binding of scuPA to suPAR also retards its cleavage by plasmin.

133 nding of Delta K-scuPA, but not WT-scuPA, to suPAR was comparably inhibited by its growth factor doma

134 of a lasting reduction in the level of total suPAR because there was no sustained significant change

135 Whether a sustained lowering of total suPAR results in further improved outcomes requires addi

136 an 40 mL/min/1.73 m2, higher log-transformed suPAR levels were associated with a higher risk of CKD p

137 We identified two suPAR-binding sites, a higher affinity site in the light

138 says revealed that soluble recombinant uPAR (suPAR) bound the Man-6-P/IGF2R at two distinct sites, on

139 3 antibodies and soluble, recombinant uPAR (suPAR), but not by antibody 7E3, which recognizes the be

140 the interaction sites between soluble uPAR (suPAR) and high molecular mass kininogen (HK).

141 of scuPA bound to recombinant, soluble uPAR (suPAR) is also fivefold less sensitive to inhibition by

142 We provide evidence that soluble uPAR (suPAR) specifically binds to integrins alpha4beta1, alph

143 ing of recombinant full-length soluble uPAR (suPAR) to scuPA with an IC50 = 253 nM and an IC50 = 1569

144 ingle (Delta K-scuPA) bound to soluble uPAR (suPAR) with the similar "on-rate" but with a faster "off

145 s abrogated by incubation with soluble uPAR (suPAR), arginine-glycine-aspartic acid (RGD)-containing

146 d release increased amounts of soluble uPAR (suPAR).

147 Urinary suPAR appears to be higher in cases of FSGS destined for

148 Urinary suPAR was indexed to creatinine.

149 However, elevated urinary suPAR showed a trend in providing additional prognostic

150 Urine suPAR was elevated in cases of recurrent FSGS compared w

151 Both serum and urine suPAR correlated with proteinuria and albuminuria.

152 We studied serum and urine suPAR from pretransplantation banked samples from 86 wel

153 st that the renal disease only develops when suPAR sufficiently activates podocyte beta(3) integrin.

154 Further studies should determine whether suPAR levels can identify children at risk for future CK

155 or uPAR(-/-) macrophages, but not both, with suPAR enhanced the uptake of viable uPAR(-/-) neutrophil

156 s 64.5% (95% CI, 57.4-71.7) in children with suPAR levels in the lowest quartile compared with 35.9%

157 egree of podocyte effacement correlates with suPAR levels at time of diagnosis.

158 Therefore, HK interacts with suPAR at several sites.

159 Incubation of uPAR(-/-) neutrophils with suPAR or anti-integrin antibodies diminished uptake by W

160 rebound was observed between sessions, with suPAR levels reaching 99 +/- 22% of the pretreatment lev

161 cell binding epitopes were generated within suPAR itself by the aminoterminal fragment of scuPA, whi