Reactive oxygen species/oxidative stress contributes to progression of kidney fibrosis following transient ischemic injury in mice.
Recently, kidney fibrosis following transplantation has become recognized as a main contributor of chronic allograft nephropathy. In transplantation, transient ischemia is an inescapable event. Reactive oxygen species (ROS) play a critical role in ischemia and reperfusion (I/R)-induced acute kidney injury, as well as progression of fibrosis in various diseases such as hypertension, diabetes, and ureteral obstruction. However, a role of ROS/oxidative stress in chronic kidney fibrosis following I/R injury remains to be defined. In this study, we investigated the involvement of ROS/oxidative stress in kidney fibrosis following kidney I/R in mice. Mice were subjected to 30 min of bilateral kidney ischemia followed by reperfusion on day 0 and then administered with either manganese (III) tetrakis(1-methyl-4-pyridyl) porphyrin (MnTMPyP, 5 mg/kg body wt ip), a cell permeable superoxide dismutase (SOD) mimetic, or 0.9% saline (vehicle) beginning at 48 h after I/R for 14 days. I/R significantly increased interstitial extension, collagen deposition, apoptosis of tubular epithelial cells, nitrotyrosine expression, hydrogen peroxide production, and lipid peroxidation and decreased copper-zinc SOD, manganese SOD, and glucose 6-phosphate dehydrogenase activities in the kidneys 16 days after the procedure. MnTMPyP administration minimized these postischemic changes. In addition, MnTMPyP administration significantly attenuated the increases of alpha-smooth muscle actin, PCNA, S100A4, CD68, and heat shock protein 47 expression following I/R. We concluded that kidney fibrosis develops chronically following I/R injury, and this process is associated with the increase of ROS/oxidative stress.
Kim
Jinu
J
Department of Anatomy and BK 21 Project, Kyungpook National University School of Medicine, Daegu, Republic of Korea.
Seok
Young Mi
YM
Jung
Kyong-Jin
KJ
Park
Kwon Moo
KM
D000199:Actins / Q000378:metabolism; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D003094:Collagen / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D005355:Fibrosis; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism; D050958:HSP47 Heat-Shock Proteins / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism; D007511:Ischemia / Q000378:metabolism* / Q000473:pathology; D007668:Kidney / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008665:Metalloporphyrins / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015427:Reperfusion Injury / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D013997:Time Factors; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D014810:Vitamin E / Q000494:pharmacology; D000097382:CD68 Molecule
D000199:Actins; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000975:Antioxidants; D003094:Collagen; D005954:Glucosephosphate Dehydrogenase; D050958:HSP47 Heat-Shock Proteins; D006861:Hydrogen Peroxide; D008665:Metalloporphyrins; D018809:Proliferating Cell Nuclear Antigen; D017382:Reactive Oxygen Species; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins; D013482:Superoxide Dismutase; D014443:Tyrosine; D014810:Vitamin E; C081026:CD68 protein, mouse; D000097382:CD68 Molecule; C502230:Mn(III) 5,10,15,20-tetrakis(N-methylpyridinium-2-yl)porphyrin; C470944:S100a4 protein, mouse; C494661:Serpinh1 protein, mouse; C002744:3-nitrotyrosine