PMID- 15780095
OWN - NLM
STAT- MEDLINE
DCOM- 20050926
LR  - 20220317
IS  - 0085-2538 (Print)
IS  - 0085-2538 (Linking)
VI  - 67
IP  - 4
DP  - 2005 Apr
TI  - A biologic role of HIF-1 in the renal medulla.
PG  - 1428-39
AB  - BACKGROUND: Activation of hypoxia-inducible factor-1 (HIF-1) is the primary 
      defensive mechanism against hypoxia. HIF-1 activation generally occurs in 
      pathologic disruption of tissue oxygenation. However, a biologic role of HIF-1 in 
      the medulla of the kidney, which is considered perpetually hypoxic under 
      physiologic conditions due to its unique circulation, remains to be elucidated. 
      METHODS: The expression of HIF-1alpha was detected by immunohistochemical 
      analysis. Functional studies of HIF in medulla were carried out by gene transfer 
      of various plasmids by retrograde injection via ureter. RESULTS: Our 
      immunohistochemical analysis detected HIF-1alpha in the inner stripe and the 
      inner medulla of normal rats. Water deprivation increased the number of 
      HIF-1alpha-positive cells, which may be mediated by an increase in medullar 
      workload and a decrease in local blood flow. To perform functional studies, we 
      performed gene transfer. Efficient expression of the transgene was confirmed 
      using an enhanced green fluorescent protein (E-GFP) expressing vector. Our 
      histologic and immunoblotting analysis detected the transgene product at the 
      inner medulla and the inner stripe 48 hours after injection. Administration of 
      negative-dominant HIF induced severe damage in the medulla of normal rats. In 
      contrast, gene transfer of constitutively active HIF (HIF/VP16) induced 
      expression of various HIF-regulated genes and protected the medulla against 
      ischemic insults. CONCLUSION: Our studies demonstrated a crucial role of HIF in 
      the renal medulla under normal and hypoxic circumstances.
FAU - Manotham, Krissanapong
AU  - Manotham K
AD  - Division of Nephrology and Endocrinology, University of Tokyo School of Medicine, 
      Tokyo, Japan.
FAU - Tanaka, Tetsuhiro
AU  - Tanaka T
FAU - Ohse, Takamoto
AU  - Ohse T
FAU - Kojima, Ichiro
AU  - Kojima I
FAU - Miyata, Toshio
AU  - Miyata T
FAU - Inagi, Reiko
AU  - Inagi R
FAU - Tanaka, Hirotoshi
AU  - Tanaka H
FAU - Sassa, Ryoji
AU  - Sassa R
FAU - Fujita, Toshiro
AU  - Fujita T
FAU - Nangaku, Masaomi
AU  - Nangaku M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Kidney Int
JT  - Kidney international
JID - 0323470
RN  - 0 (DNA Primers)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Hif1a protein, rat)
RN  - 0 (Hypoxia-Inducible Factor 1)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Transcription Factors)
RN  - 147336-22-9 (Green Fluorescent Proteins)
SB  - IM
MH  - Animals
MH  - Apoptosis
MH  - Blood Urea Nitrogen
MH  - Cell Hypoxia/physiology
MH  - DNA Primers
MH  - DNA-Binding Proteins/genetics/*physiology
MH  - Gene Transfer Techniques
MH  - Genes, Reporter
MH  - Green Fluorescent Proteins/genetics
MH  - Hypoxia-Inducible Factor 1
MH  - Hypoxia-Inducible Factor 1, alpha Subunit
MH  - Kidney Medulla/cytology/*physiology
MH  - Nuclear Proteins/genetics/*physiology
MH  - Polymerase Chain Reaction
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Transcription Factors/analysis/genetics/*physiology
EDAT- 2005/03/23 09:00
MHDA- 2005/09/27 09:00
CRDT- 2005/03/23 09:00
PHST- 2005/03/23 09:00 [pubmed]
PHST- 2005/09/27 09:00 [medline]
PHST- 2005/03/23 09:00 [entrez]
AID - S0085-2538(15)50598-X [pii]
AID - 10.1111/j.1523-1755.2005.00220.x [doi]
PST - ppublish
SO  - Kidney Int. 2005 Apr;67(4):1428-39. doi: 10.1111/j.1523-1755.2005.00220.x.