PMID- 20219823
OWN - NLM
STAT- MEDLINE
DCOM- 20100614
LR  - 20181113
IS  - 1522-1466 (Electronic)
IS  - 1931-857X (Print)
IS  - 1522-1466 (Linking)
VI  - 298
IP  - 6
DP  - 2010 Jun
TI  - Omi/HtrA2 protease is associated with tubular cell apoptosis and fibrosis induced 
      by unilateral ureteral obstruction.
PG  - F1332-40
LID - 10.1152/ajprenal.00737.2009 [doi]
AB  - Kidney fibrosis, a typical characteristic of chronic renal disease, is associated 
      with tubular epithelial cell apoptosis. The results of our recent studies have 
      shown that Omi/HtrA2 (Omi), a proapoptotic mitochondrial serine protease, 
      performs a crucial function in renal tubular epithelial apoptotic cell death in 
      animal models of acute kidney injury, including cisplatin toxicity and 
      ischemia-reperfusion insult. However, the role of Omi in tubulointerstitial 
      disease-associated fibrosis in the kidney remains to be clearly defined. We 
      evaluated the potential function and molecular mechanism of Omi in ureteral 
      obstruction-induced kidney epithelial cell apoptosis and fibrosis. The mice were 
      subjected to unilateral ureteral obstruction (UUO) via the ligation of the left 
      ureter near the renal pelvis. UUO increased the protein level of Omi in the 
      cytosolic fraction of the kidney, with a concomitant reduction in the 
      mitochondrial fraction. UUO reduced the X-linked inhibitor of apoptosis protein 
      (XIAP), a substrate of Omi, and pro-caspase-3, whereas it increased cleaved 
      poly(ADP-ribose) polymerase (cleaved PARP) and the number of terminal 
      deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL)-positive cells. When 
      mice were treated with ucf-101, an inhibitor of the proteolytic activity of Omi 
      (6.19 microg/day ip), on a daily basis beginning 2 days before UUO and continuing 
      until the end of the experiment, the Omi inhibitor protected XIAP cleavage after 
      UUO and reduced the increment of PARP cleavage and the numbers of TUNEL-positive 
      cells. Furthermore, the Omi inhibitor significantly attenuated UUO-induced 
      increases in fibrotic characteristics in the kidney, including the atrophy and 
      dilation of tubules, expansion of the interstitium, and increases in the 
      expression of collagens, alpha-smooth muscle actin, and fibronectin. In 
      conclusion, Omi/HtrA2 is associated with apoptotic signaling pathways in tubular 
      epithelial cells activated by unilateral ureteral obstruction, thereby resulting 
      in kidney fibrosis.
FAU - Kim, Jinu
AU  - Kim J
AD  - Department of Anatomy, Kyungpook National University School of Medicine, Daegu, 
      Republic of Korea.
FAU - Kim, Dong Sun
AU  - Kim DS
FAU - Park, Mae Ja
AU  - Park MJ
FAU - Cho, Hee-Jung
AU  - Cho HJ
FAU - Zervos, Antonis S
AU  - Zervos AS
FAU - Bonventre, Joseph V
AU  - Bonventre JV
FAU - Park, Kwon Moo
AU  - Park KM
LA  - eng
GR  - R01 DK072381/DK/NIDDK NIH HHS/United States
GR  - DK055734/DK/NIDDK NIH HHS/United States
GR  - DK39773/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20100310
PL  - United States
TA  - Am J Physiol Renal Physiol
JT  - American journal of physiology. Renal physiology
JID - 100901990
RN  - 0 (Acta2 protein, mouse)
RN  - 0 (Actins)
RN  - 0 (Mitochondrial Proteins)
RN  - 0 (Protease Inhibitors)
RN  - 0 (Pyrimidinones)
RN  - 0 (Thiones)
RN  - 0 (UCF 101)
RN  - 0 (X-Linked Inhibitor of Apoptosis Protein)
RN  - EC 2.4.2.30 (Poly(ADP-ribose) Polymerases)
RN  - EC 3.4.21.- (Serine Endopeptidases)
RN  - EC 3.4.21.108 (High-Temperature Requirement A Serine Peptidase 2)
RN  - EC 3.4.21.108 (Htra2 protein, mouse)
RN  - EC 3.4.22.- (Casp3 protein, mouse)
RN  - EC 3.4.22.- (Caspase 3)
SB  - IM
MH  - Actins/metabolism
MH  - Animals
MH  - *Apoptosis/drug effects
MH  - Caspase 3/metabolism
MH  - Disease Models, Animal
MH  - Epithelial Cells/enzymology
MH  - Fibrosis
MH  - High-Temperature Requirement A Serine Peptidase 2
MH  - In Situ Nick-End Labeling
MH  - Kidney Diseases/*enzymology/etiology/pathology/prevention & control
MH  - Kidney Tubules/drug effects/*enzymology/pathology
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mitochondria/enzymology
MH  - Mitochondrial Proteins/antagonists & inhibitors/*metabolism
MH  - Poly(ADP-ribose) Polymerases/metabolism
MH  - Protease Inhibitors/pharmacology
MH  - Pyrimidinones/pharmacology
MH  - Serine Endopeptidases/*metabolism
MH  - Signal Transduction
MH  - Thiones/pharmacology
MH  - Time Factors
MH  - Ureteral Obstruction/complications/drug therapy/*enzymology/pathology
MH  - X-Linked Inhibitor of Apoptosis Protein/metabolism
PMC - PMC2886814
EDAT- 2010/03/12 06:00
MHDA- 2010/06/15 06:00
PMCR- 2011/06/01
CRDT- 2010/03/12 06:00
PHST- 2010/03/12 06:00 [entrez]
PHST- 2010/03/12 06:00 [pubmed]
PHST- 2010/06/15 06:00 [medline]
PHST- 2011/06/01 00:00 [pmc-release]
AID - 00737.2009 [pii]
AID - F-00737-2009 [pii]
AID - 10.1152/ajprenal.00737.2009 [doi]
PST - ppublish
SO  - Am J Physiol Renal Physiol. 2010 Jun;298(6):F1332-40. doi: 
      10.1152/ajprenal.00737.2009. Epub 2010 Mar 10.