PMID- 10322639
OWN - NLM
STAT- MEDLINE
DCOM- 19990701
LR  - 20141120
IS  - 0192-253X (Print)
IS  - 0192-253X (Linking)
VI  - 24
IP  - 3-4
DP  - 1999
TI  - Developmental expression of urine concentration-associated genes and their
      altered expression in murine infantile-type polycystic kidney disease.
PG  - 309-18
AB  - Currently, there is little understanding of what factors regulate the development
      of urine concentrating capability in normal or polycystic kidney. The present
      study examined the developmental expression of genes associated with urine
      concentration in developing mice, including C57BL/6J-cpk/cpk mice with autosomal 
      recessive-infantile (AR) polycystic kidney disease (PKD). Concentration of urine 
      requires: 1) medullary collecting ducts (CD) located within a hypertonic
      interstitium, 2) CD cell expression of functional arginine vasopressin V2
      receptors (AVP-V2R), and 3) the presence of appropriate CD water channels
      (aquaporins, AQP 2 and 3). An increase in urine osmolarity, normally seen between
      1 and 3 weeks of age, was absent in cpk cystic mice. Aldose reductase mRNA
      expression (a gene upregulated by medullary hyperosmolarity) increased in normal 
      mice, but remained low in the cystic kidney, suggesting the absence of a
      hypertonic medullary interstitium. AVP-V2R, AQP2, and AQP3 mRNA expression
      normally increase between 7 and 14 days. However, all were dramatically
      overexpressed even at 7 days of age in the cpk kidney in vivo, but decreased in
      vitro. Activation of the AVP-V2 receptor stimulates the production of cAMP, a
      substance known to promote cyst enlargement. To determine if CD cAMP, generated
      from increased AVP-V2Rs, was accelerating the PKD, cystic mice and their normal
      littermates were treated with OPC31260, a relatively specific AVP-V2R antagonist.
      OPC31260 treatment of cystic mice led to an amelioration of the cystic
      enlargement and azotemia. Treatment also decreased renal AQP2 mRNA but increased 
      AVP-V2R and AQP3 mRNA expression in vivo. AVP upregulates the expression of
      AVP-V2R, AQP2, and AQP3 mRNAs in vitro. Renal EGF, known to inhibit AVP-V2R
      activity, downregulates AVP-V2R mRNA in vitro. Brief in vivo EGF treatment, known
      to decrease PKD in cpk mice, led to increased expression of AVP-V2R, AQP2, and
      AQP3 mRNAs at 2 weeks in both normal and cystic mice but no change was evident at
      3 weeks of age. In conclusion, the development of urinary concentration ability
      correlates with the development of an increased medullary osmotic gradient which 
      is diminished in murine ARPKD. However, CD genes associated with this process are
      overexpressed in vivo but underexpressed in vitro in the cystic kidney. The
      overexpression and/or overactivity of the AVP-V2R appears to contribute to the
      progression of PKD since an AVP-V2R antagonist inhibits cystic renal enlargement 
      in the cpk mouse.
FAU - Gattone, V H 2nd
AU  - Gattone VH 2nd
AD  - Department of Anatomy and Cell Biology, University of Kansas Medical Center,
      Kansas City 66160-7400, USA. vgattone@kumc.edu
FAU - Maser, R L
AU  - Maser RL
FAU - Tian, C
AU  - Tian C
FAU - Rosenberg, J M
AU  - Rosenberg JM
FAU - Branden, M G
AU  - Branden MG
LA  - eng
GR  - DK40695/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Dev Genet
JT  - Developmental genetics
JID - 7909963
RN  - 0 (Antidiuretic Hormone Receptor Antagonists)
RN  - 0 (Aqp2 protein, mouse)
RN  - 0 (Aqp3 protein, mouse)
RN  - 0 (Aquaporin 2)
RN  - 0 (Aquaporin 6)
RN  - 0 (Aquaporins)
RN  - 0 (Benzazepines)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Vasopressin)
RN  - 158801-98-0 (Aquaporin 3)
RN  - 17OJ42922Y (mozavaptan)
RN  - EC 1.1.1.21 (Aldehyde Reductase)
SB  - IM
MH  - Aldehyde Reductase/genetics
MH  - Animals
MH  - Antidiuretic Hormone Receptor Antagonists
MH  - Aquaporin 2
MH  - Aquaporin 3
MH  - Aquaporin 6
MH  - Aquaporins/genetics
MH  - Benzazepines/pharmacology
MH  - Female
MH  - Gene Expression Regulation, Developmental
MH  - Kidney Concentrating Ability/*genetics
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Mutant Strains
MH  - Polycystic Kidney, Autosomal Recessive/*genetics/physiopathology
MH  - RNA, Messenger/genetics/metabolism
MH  - Receptors, Vasopressin/genetics
EDAT- 1999/05/14 02:02
MHDA- 2000/06/20 09:00
CRDT- 1999/05/14 02:02
PHST- 1999/05/14 02:02 [pubmed]
PHST- 2000/06/20 09:00 [medline]
PHST- 1999/05/14 02:02 [entrez]
AID - 10.1002/(SICI)1520-6408(1999)24:3/4<309::AID-DVG14>3.0.CO;2-5 [pii]
AID - 10.1002/(SICI)1520-6408(1999)24:3/4<309::AID-DVG14>3.0.CO;2-5 [doi]
PST - ppublish
SO  - Dev Genet. 1999;24(3-4):309-18. doi:
      10.1002/(SICI)1520-6408(1999)24:3/4<309::AID-DVG14>3.0.CO;2-5.