Stathmin-deficient mice develop fibrosis and show delayed recovery from ischemic-reperfusion injury.
In kidneys subjected to ischemic reperfusion injury (IRI) stathmin, a tubulin-binding protein involved in the regulation of mitosis, is expressed in dedifferentiated and proliferating renal tubule cells during the recovery phase. To ascertain the role of stathmin in the recovery from ischemic kidney injury, stathmin-deficient (OP18-/-) and wild-type (WT) animals were subjected to experimental IRI. At 3, 7, and 14 days after reperfusion serum samples and kidneys were collected for the examination of parameters of renal function, morphology, and recovery. Our studies indicate that on day 14 after reperfusion OP18-/- mice have significant renal failure, whereas the creatinine levels of WT animals have returned to baseline. Compared with WT animals OP18-/- mice had more extensive tubular fibrosis. The examination of proliferating cell nuclear antigen expression indicated that OP18-/- animals have increased proliferative or DNA repair activity for a more prolonged duration. The OP18-/- animals also had an increased number of tubules with apoptotic cells. These results suggest that in stathmin-deficient mice subjected to IRI, the aberrant regulation of cell cycle progression, not observed under normal conditions, impairs or at least delays the process of tubular repair and recovery after acute renal injury.
Zahedi
Kamyar
K
Division of Nephrology and Hypertension, Children's Hospital Medical Center, Cincinnati, OH 45229-3039, USA. Kamyar.Zahedi@cchmc.org
Revelo
Monica P
MP
Barone
Sharon
S
Wang
Zhaohui
Z
Tehrani
Kathy
K
Citron
David P
DP
Bissler
John J
JJ
Rabb
Hamid
H
Soleimani
Manoocher
M
D000818:Animals; D017209:Apoptosis; D002455:Cell Division; D004260:DNA Repair; D004847:Epithelial Cells / Q000737:chemistry / Q000473:pathology; D005355:Fibrosis; D007178:Inbreeding; D007668:Kidney / Q000098:blood supply* / Q000473:pathology / Q000503:physiopathology; D007684:Kidney Tubules / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D051437:Renal Insufficiency / Q000453:epidemiology / Q000209:etiology; D015427:Reperfusion Injury / Q000401:mortality / Q000473:pathology / Q000503:physiopathology*; D050777:Stathmin / Q000172:deficiency* / Q000235:genetics / Q000502:physiology*; D015431:Weight Loss
D018809:Proliferating Cell Nuclear Antigen; D050777:Stathmin