Modulation of peripheral-type benzodiazepine receptor during ischemia reperfusion injury in a pig kidney model: a new partner of leukemia inhibitory factor in tubular regeneration.
BACKGROUND
It was demonstrated that postischemic kidney expresses different factors in a pattern that recapitulates expression of these factors in the developing kidney. We investigated whether peripheral-type benzodiazepine receptor (PBR), which belongs to the mitochondrial permeability transition pore and is essential during development, could be influenced by the ischemia-reperfusion injury process when compared with leukemia inhibitor factor (LIF).


METHODS
PBR, LIF, and LIF receptor messengers and proteins were analyzed in adult normal and ischemic kidney under conditions mimicking cardiac arrest: 18 pigs were studied after 60 minutes of warm ischemia and reperfusion for 7 days and compared with sham-operated (Sham, n = 12) and control (CONT, n = 12) groups. The same messengers and proteins were assessed in fetal kidneys.


RESULTS
In normal kidney, PBR was expressed in descending and ascending limbs of Henle and in distal tubules. After ischemia-reperfusion injury, PBR mRNA significantly increased between days 1 and 7 in cortex and outer medulla. PBR protein increased between days 1 and 7, and was transiently expressed in proximal tubules at days 1 and 3 and returned to basal level at day 7. LIF messenger and protein increased rapidly at day 1 in proximal tubules. In turn, LIF receptor messenger and protein were not changed during reperfusion.


CONCLUSIONS
These results suggest that PBR may be implicated in ischemia-reperfusion injury and, particularly, in the regenerative process within proximal tubules with LIF. These new insights open the possibility of novel targets for organ protection and repair.
Zhang
Keqiang
K
INSERM ERM 324 and Faculté de Médecine, Poitiers, France.
Desurmont
Thibault
T
Goujon
Jean Michel
JM
Favreau
Frederic
F
Cau
Jerôme
J
Deretz
Séverine
S
Mauco
Gérard
G
Carretier
Michel
M
Papadopoulos
Vassilios
V
Hauet
Thierry
T
D000818:Animals; D015850:Interleukin-6 / Q000032:analysis / Q000502:physiology*; D007668:Kidney / Q000098:blood supply* / Q000737:chemistry*; D007684:Kidney Tubules / Q000502:physiology*; D053605:Leukemia Inhibitory Factor; D008297:Male; D011506:Proteins / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis; D011963:Receptors, GABA-A / Q000032:analysis / Q000502:physiology*; D012038:Regeneration / Q000502:physiology*; D015427:Reperfusion Injury / Q000378:metabolism*; D013552:Swine
D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D011506:Proteins; D012333:RNA, Messenger; D011963:Receptors, GABA-A