ライフサイエンスコーパス: AQP3

1 uamous cell carcinoma strongly overexpresses AQP3.

2 t migration induced lysosomal degradation of AQP3.

3 investigate HDAC's role in the regulation of AQP3.

4 versed MPXR in cells lacking native AQP2 and AQP3.

5 x 10(-14)) 3.3 +/- 0.2 (AQP2), 2.1 +/- 0.3 (AQP3), 24 +/- 0.6 (AQP4), 5.0 +/- 0.4 (AQP5), and 0.25 +

6 , 19 +/- 2 (AQP1), 10 +/- 1 (AQP2), 8 +/- 2 (AQP3), 29 +/- 1 (AQP4), 10 +/- 1 (AQP5), and 1.3 +/- 0.2

7 nto the cell by transit through aquaporin-3 (AQP3), a plasma membrane H2O2-conducting channel.

8 Aquaporin 3 (AQP3), a water/glycerol channel protein, has been found

9 In keratinocytes aquaporin-3 (AQP3), an efficient glycerol transporter, is associated

10 e protein kinase A, inducing localization of AQP3 and AQP2 at the leading edge and increasing the mig

11 langiocytes, AQP4 in gastric parietal cells, AQP3 and AQP4 in colonic surface epithelium, AQP5 in sal

12 d Z433927330 constitute selective and potent AQP3 and AQP7 inhibitors, respectively, and contribute t

13 Consistent with the known functions of Aqp3 and Aqp8 as H2O2 transporters, primitive, but not d

14 irectly demonstrates that aquaporin isoforms AQP3 and AQP8, but not AQP1, can promote uptake of H(2)O

15 The use of hydrogen peroxide altered AQP3 and NOTCH1 expression, and the use of N-acetyl-L-cy

16 our laboratory has shown co-localization of AQP3 and phospholipase D2 (PLD2) in caveolin-rich membra

17 ) in response to TNF-alpha is facilitated by AQP3 and required for NF-kappaB activation by regulation

18 re the same pathway with glycerol or urea in AQP3 and that this aquaporin, therefore, forms a water-s

19 psoriasis is reduced in AQP3 knockout mice (AQP3(-/-)), and is accompanied by impaired NF-kappaB act

20 terminal fragments of TMC1 with Aquaporin 3 (AQP3) and GFP fusion reporter, which intrinsically label

21 icant decrease in protein abundance of AQP2, AQP3, and AQP4 in HT rats as compared with CTL and HT+T

22 cending limb of Henle, and vasa recta; AQP2, AQP3, and AQP4 in the collecting duct; AQP6 in the papil

23 of mice lacking kidney water channels AQP1, AQP3, and AQP4 indicates a critical role for AQP2 in neo

24 nd on knockout mice lacking aquaporins AQP1, AQP3, and AQP5.

25 an control rats despite an increase in AQP1, AQP3, and Na-K-2Cl co-transporter expression.

26 d increased abundance of aquaporin 1 (AQP1), AQP3, and Na-K-2Cl co-transporter proteins and a marked

27 leading to water influx, potentially through AQP3, and that water influx is required for TCR-induced

28 genic null mice lacking (individually) AQP1, AQP3, AQP4, and AQP5.

29 edullary collecting-duct water channel AQP4, AQP3/AQP4 double-knockout mice were generated.

30 uaglyceroporins, encoded by the aquaporin 3 (Aqp3), Aqp7, and Aqp9 genes in mouse islets.

31 Multifunctional aquaglyceroporins AQP3, AQP7, and AQP9 are permeated by water, glycerol, a

32 Molecular docking to AQP3, AQP7, and AQP9 homology models suggested interacti

33 AQP1 and AQP3 are also expressed in the kidney where their deleti

34 These findings implicate AQP3 as a novel determinant of renal cyst enlargement an

35 Recent data implicate AQP3 as an important determinant in epidermal proliferat

36 As AQP3 associates with Nox2, we propose that this interpla

37 addition, phloretin (0.1 mM) inhibited Pf of AQP3 by 35%, whereas it did not alter Pgly or Pur.

38 e report that the water channel Aquaporin-3 (AQP3) can facilitate the uptake of H(2)O(2) into mammali

39 The mouse AQP3 cDNA was isolated and encodes a 292-amino acid wate

40 ells irreversibly, while Ni (2+) blocked the AQP3 channels reversibly.

41 AQP3 coexpression decreased the promoter activity of ker

42 gged AQP3 (GLIP) and each of the four tagged AQP3 constructs; [3H]glycerol uptake was not increased i

43 d using polyclonal antibodies to rat AQP2 or AQP3 (courtesy of Dr. M.A. Knepper, National Institutes

44 AQP3 deficiency did not alter corneal epithelial thickne

45 st that the slowed renal cyst enlargement in AQP3 deficiency involves impaired energy metabolism in t

46 glycerol-3-phosphate, and ATP were found in AQP3 deficiency without impairment of mitochondrial func

47 the reduced proliferation and ATP content in AQP3 deficiency, with cellular glycerol, ATP, and prolif

48 AQP3 deficient (AQP3(-/-)) mice exhibited significantly

49 Reduced AQP3-dependent glycerol transport in AQP3-deficient epidermis appears to be responsible for t

50 AQP3-deficient kidneys showed significantly reduced ATP

51 tion in proliferating BrdU-positive cells in AQP3-deficient mice during healing, and by reduced proli

52 mpairment in corneal re-epithelialization in AQP3-deficient mice results from distinct defects in cor

53 ) = 0.025 cm/s), slowing 3.6 +/- 0.7-fold in AQP3-deficient mice.

54 hanical, and biosynthetic defects in skin of AQP3-deficient mice.

55 AQP3 deletion did not affect erythrocyte glycerol permea

56 By electron microscopy AQP3 deletion did not affect the structure of the unpert

57 AQP3 deletion had little effect on AQP1 or AQP4 protein

58 a, lactic acid, glucose) was not affected by AQP3 deletion nor was the absolute amount or profile of

59 asal skin barrier function was not impaired, AQP3 deletion produced an approximately 2-fold delay in

60 However, AQP3 deletion produced significant reductions in glycero

61 AQP3 deletion resulted in a > 4-fold reduced osmotic wat

62 stinct defect in cell migration arising from AQP3 deletion.

63 iva was 0.0011 cm/s and was not sensitive to AQP3 deletion.

64 le Pkd1 knockout mice, each without and with AQP3 deletion.

65 ng, was also approximately 2-fold delayed by AQP3 deletion.

66 and morphology were not grossly affected by AQP3 deletion.

67 tering optics method, was >3-fold reduced by AQP3 deletion.

68 components with E-cadherin, but each blocked AQP3 delivery to forming cell-cell contacts.

69 Reduced AQP3-dependent glycerol transport in AQP3-deficient epid

70 e burns accelerated their healing through an AQP3-dependent mechanism that activates angiogenesis, tr

71 In response to injury, AQP3-depleted colonic epithelial cells showed defective

72 in the selectivity filters of AQP1, AQP4 and AQP3 differentially affect glycerol and urea permeabilit

73 While AQP3 disappeared within the first 2-3 rows of cells, AQP

74 Daily urine output in AQP1/AQP3 double knockout mice (15 ml) was 9-fold greater tha

75 Here AQP1/AQP3 double knockout mice were generated and analyzed to

76 Hg (2+) inhibited the water flux in AQP3-expressing cells irreversibly, while Ni (2+) blocke

77 reduced in AQP3-null PKD mice compared with AQP3-expressing PKD mice, with the difference seen mainl

78 C3 suggested a role for HDAC3 in suppressing AQP3 expression basally.

79 Thus, our study supports the regulation of AQP3 expression by HDAC3 and p53.

80 However, AQP3 expression has not been observed in mouse erythrocy

81 AQP3 expression in human skin is increased in response t

82 (4), we obtained evidence for involvement of AQP3 expression in nuclear factor-kappaB (NF-kappaB) cel

83 cells in the collecting duct, and increased AQP3 expression in the basolateral membrane.

84 Modulation of AQP3 expression or function may thus alter epidermal moi

85 -grown Madin-Darby canine kidney cyst model, AQP3 expression promoted cyst enlargement and was associ

86 be modulated up or down based on endogenous AQP3 expression, which in turn can influence downstream

87 nvolved in regulating HDAC inhibitor-induced AQP3 expression.

88 release and found a significant increase in AQP3 expression.

89 The contribution of AQP3-facilitated cell migration to corneal re-epithelial

90 Our data suggest involvement of AQP3-facilitated glycerol transport in epidermal cell pr

91 QP3 monoclonal antibody (mAb) that inhibited AQP3-facilitated H(2)O(2) and glycerol transport, and pr

92 Collectively, these data indicate that AQP3-facilitated H2O2 transport is required for NF-kappa

93 Both AQP2 and AQP3 gained access to the surface plasma membrane in ins

94 esis was discovered using mice with targeted AQP3 gene disruption.

95 The mouse AQP3 gene was analyzed, and AQP3 null mice were generate

96 over control) in oocytes expressing untagged AQP3 (GLIP) and each of the four tagged AQP3 constructs;

97 nfirmed that DFP00173 and Z433927330 inhibit AQP3 glycerol permeability in human erythrocytes.

98 Re-expression of AQP3 had no effect on the expression of the proliferatio

99 Thus, our results indicate that AQP3 has a pro-differentiative role in epidermal keratin

100 Aquaporin (AQP) water channel AQP3 has been proposed to be the major glycerol and non-

101 Aquaporin-3 (AQP3) has an important physiological function in renal w

102 rmal water/glycerol transporter aquaporin-3 (AQP3) have reduced stratum corneum (SC) hydration and sk

103 These results imply a critical role of AQP3 in asthma, and AQP3 may be a novel therapeutic targ

104 udies indicate independent roles of AQP1 and AQP3 in countercurrent exchange and collecting duct osmo

105 To study the role of AQP3 in cyst development, we generated 2 polycystic kidn

106 Involvement of AQP3 in epithelial cell proliferation was investigated b

107 alyzed to investigate the functional role of AQP3 in erythrocytes and kidneys.

108 preclude surface localization of PM protein AQP3 in HEK293 cells.

109 H2O2 in the colonic epithelium and implicate AQP3 in innate immunity at mucosal surfaces.

110 udies, controversy remains about the role of AQP3 in keratinocyte differentiation.

111 ings implicate the involvement of macrophage AQP3 in liver injury, and provide evidence for mAb inhib

112 To test this idea, we re-expressed AQP3 in mouse keratinocytes derived from AQP3-knockout m

113 inappropriate expression of Tgm1, Krt16, and Aqp3 In parallel, HDAC3 suppresses expression of inflamm

114 t functional evidence for the involvement of AQP3 in skin physiology.

115 A novel role for AQP3 in skin tumorigenesis was discovered using mice wit

116 We studied the role of AQP3 in stratum corneum (SC) hydration by comparative me

117 -2 (AQP2), phosphorylated AQP2 (p-AQP2), and AQP3 in the inner medulla and in the outer medulla plus

118 rmal water/glycerol transporter aquaporin-3 (AQP3) in mice reduced superficial skin conductance by ap

119 he isoforms AQP1 and AQP4 decreased, whereas AQP3 increased, levels of plasma membrane-associated lat

120 in vivo and vitro experiments indicated that AQP3 induced the production of some chemokines such as C

121 aquaporin in cell proliferation and suggest AQP3 induction as a possible therapy to accelerate the r

122 ylurea-linked compound Z433927330, a partial AQP3 inhibitor (IC(50), ~0.7-0.9 mum), is a potent and e

123 rapy for skin diseases like psoriasis, where AQP3 is abnormally expressed.

124 Our data provide direct evidence that AQP3 is not functionally important in erythrocyte water

125 Finally, we establish that AQP3 is required for Nox-derived H(2)O(2) signaling upon

126 AQP3 is the AQP that is expressed in the skin where it f

127 AQP3 is thus a key player in epidermal biology and a pot

128 ; (b) AQP2 is unchanged in the base; and (c) AQP3 is unchanged.

129 Aquaporin-3 (AQP3) is a membrane transporter of water and glycerol ex

130 Aquaporin-3 (AQP3) is a small transmembrane water/glycerol channel th

131 Aquaporin 3 (AQP3) is a transporter of water, glycerol and hydrogen p

132 Aquaporin-3 (AQP3) is a water and glycerol channel expressed in epide

133 Aquaporin-3 (AQP3) is a water channel expressed at the basolateral pl

134 Aquaporin-3 (AQP3) is a water channel found in the basolateral cell m

135 Aquaporin-3 (AQP3) is a water/glycerol-transporting protein expressed

136 Here, we show that H2O2, imported via AQP3, is involved in nuclear factor-kappaB (NF-kappaB) s

137 ediated induction of psoriasis is reduced in AQP3 knockout mice (AQP3(-/-)), and is accompanied by im

138 Using AQP3 knockout mice in a model of liver injury and fibros

139 d [(3)H]glycerol uptake in normal but not in AQP3-knockout keratinocytes, confirming that the express

140 oliferation and skin tumorigenesis, in which AQP3-knockout mice are resistant to tumor formation by a

141 AQP3-knockout mice have reduced stratum corneum water co

142 content in epidermis and stratum corneum in AQP3-knockout mice, and correction of the phenotype abno

143 sed AQP3 in mouse keratinocytes derived from AQP3-knockout mice.

144 us, TCR signaling via WNK1, OXSR1, STK39 and AQP3 leads to water entry that is essential for CD4(+) T

145 The SAHA-induced increase in AQP3 levels resulted in enhanced [(3)H]glycerol uptake i

146 Administration of an anti-AQP3 mAb, which targeted an extracellular epitope on AQP

147 imply a critical role of AQP3 in asthma, and AQP3 may be a novel therapeutic target.

148 AQP3 may thus be an important determinant in skin tumori

149 QP3, prevented liver injury by inhibition of AQP3-mediated H(2)O(2) transport and macrophage activati

150 , and provide evidence for mAb inhibition of AQP3-mediated H(2)O(2) transport as therapy for macropha

151 ng to liver injury, by a mechanism involving AQP3-mediated H(2)O(2) transport.

152 al function in renal water reabsorption, and AQP3-mediated hydrogen peroxide (H(2)O(2)) permeability

153 ce receiving OVA-sensitized splenocytes from AQP3(-/-) mice compared with wild-type mice after OVA ch

154 consistently with fewer CD4(+) T cells from AQP3(-/-) mice migrating to the lung than from wild-type

155 hogen Citrobacter rodentium Correspondingly, AQP3(-/-) mice showed impaired healing of superficial wo

156 AQP3 deficient (AQP3(-/-)) mice exhibited significantly reduced airway i

157 Here, we developed an anti-AQP3 monoclonal antibody (mAb) that inhibited AQP3-facil

158 itor suberoylanilide hydroxamic acid induced AQP3 mRNA and protein expression in a dose- and time-dep

159 cells potentiated the expression of AQP2 and AQP3 mRNA, and cAMP production induced by dDAVP (desmopr

160 lly corrected the reduced skin elasticity in AQP3 null mice as measured by the kinetics of skin displ

161 The renal medulla in most AQP1/AQP3 null mice by age 4 weeks was atrophic and fluid-fil

162 by comparative measurements in wild-type and AQP3 null mice generated in a hairless SKH1 genetic back

163 The hairless AQP3 null mice had normal perinatal survival, growth, an

164 city, barrier recovery, and wound healing in AQP3 null mice in a hairless (SKH1) genetic background a

165 howed remarkably reduced SC water content in AQP3 null mice in the hairless genetic background (165 +

166 tion in epidermal and SC glycerol content in AQP3 null mice may account for these defects, providing

167 The impaired skin hydration in AQP3 null mice provides the first functional evidence fo

168 s that the residual concentrating ability of AQP3 null mice was due to the inner medullary collecting

169 Fluid consumption in AQP3 null mice was more than 10-fold greater than that i

170 SC hydration in hairless wild-type and AQP3 null mice was reduced to comparable levels (90-100

171 sin administration or water deprivation, the AQP3 null mice were able to concentrate their urine part

172 The mouse AQP3 gene was analyzed, and AQP3 null mice were generated by targeted gene disruptio

173 The growth and phenotype of AQP3 null mice were grossly normal except for polyuria.

174 ed by cutometry was significantly reduced in AQP3 null mice with approximately 50% reductions in elas

175 reduced blood-to-SC transport of glycerol in AQP3 null mice, resulting in slowed lipid biosynthesis.

176 SC glycerol content is reduced 3-fold in AQP3 null mice, whereas SC structure, protein/lipid comp

177 replacement corrects each of the defects in AQP3 null mice.

178 d reduced water content throughout the SC in AQP3 null mice.

179 content was reduced by approximately 50% in AQP3 null mice.

180 reduced water holding capacity in the SC of AQP3 null mice.

181 QP1 deletion but not further reduced in AQP1/AQP3 null mice.

182 e and 3H2O accumulation, was 3-fold lower in AQP3 null vs. wild-type mice, but became similar after t

183 ll proliferation was greatly impaired in the AQP3-null epidermis.

184 ization in vivo was significantly delayed in AQP3-null mice compared to wild-type mice.

185 d restoration of full-thickness epithelia of AQP3-null mice over days after scraping suggested a sepa

186 lities were measured in living wild-type and AQP3-null mice using calcein fluorescence-quenching and

187 We found that AQP3-null mice were remarkably resistant to the developm

188 parable apoptotic responses in wild-type and AQP3-null mice, promoter-induced cell proliferation was

189 rneal epithelial cells from wild-type versus AQP3-null mice.

190 ry cultures of corneal epithelial cells from AQP3-null mice.

191 d cyst indexes were significantly reduced in AQP3-null PKD mice compared with AQP3-expressing PKD mic

192 e found expression of Aqp7 only, not that of Aqp3 or Aqp9, in the endocrine pancreas at both the mRNA

193 sfection experiments were performed in which AQP3 or empty vector was introduced into keratinocytes s

194 as ABR thresholds were not affected by AQP1, AQP3, or AQP5 deletion.

195 293) cells were transiently transfected with AQP3- or AQP4-encoding genes to express AQPs in plasma m

196 itized variants functionally associated with AQP3 (P = 2.7 x 10-8) and ARHGAP33 (P = 1.3 x 10-8), res

197 Here we report that AQP3 potentiates ovalbumin (OVA)-induced murine asthma b

198 , which targeted an extracellular epitope on AQP3, prevented liver injury by inhibition of AQP3-media

199 l trafficking of AQP2, p-AQP2, and increased AQP3 protein expression.

200 2 (AQP2, the AVP-regulated water channel) or AQP3 protein was altered.

201 sphatidylglycerol (PG), we hypothesized that AQP3 provides glycerol to PLD2 for PG synthesis, which t

202 ot a LD PLD1 mutant, significantly inhibited AQP3 re-expression-induced differentiation marker expres

203 with 6.0 and 2.3 for water channels AQP1 and AQP3, respectively.

204 genes coding for the channel proteins Aqp2, Aqp3, Scnn1b (ENaCbeta), and Scnn1g (ENaCgamma), which a

205 Interestingly, overexpression of AQP1 and AQP3 showed no differences in extracellular signal-regul

206 f urinary-concentrating ability than did the AQP3 single-knockout mice.

207 Thus, our results support the idea that AQP3 supplies PLD2 with glycerol for synthesizing PG, a

208 For AQP3 the Arrhenius energy of activation for Pf was 3 kca

209 To examine the selectivity of AQP3, the permeability to water (Pf), urea (Pur), and gl

210 ferentiative signal, such that the action of AQP3 to induce differentiation should require PLD2.

211 estigation that examined the contribution of AQP3 to the mechanism of EPO action on the healing of bu

212 Acidic medium inhibits AQP3 transport activity; both glycerol uptake and PG syn

213 We hypothesized that AQP3 transports glycerol and "funnels" this primary alco

214 keratinocytes, confirming that the expressed AQP3 was functional.

215 e uptake of glycerol into oocytes expressing AQP3 was linear up to 165 mM.

216 Xenopus oocytes injected with cRNA encoding AQP3 was measured.

217 it water flow across the cell membrane, only AQP3 was permeable to glycerol and urea (Pgly > Pur).

218 all solute-transporting protein aquaporin-3 (AQP3) was found by immunofluorescence and immunogold ele

219 closely related aquaglyceroporins, AQP2 and AQP3, was linked to MPXR in a high-throughput loss-of-fu

220 like small molecules for inhibition of mouse AQP3 water permeability.

221 ercuriphenylsulfonate (1 mM) abolished Pf of AQP3, whereas it did not affect Pgly.

222 The re-expression of AQP3, which increased [3H]glycerol uptake, also induced

223 nd DFP00173, which inhibited mouse and human AQP3 with an IC(50) of ~0.1-0.4 mum but had low efficacy