Peritubular capillary preservation with COMP-angiopoietin-1 decreases ischemia-reperfusion-induced acute kidney injury.
Ischemia followed by reperfusion induces microvascular endothelial cell injury, leading to the loss of functions such as regulation of vascular tone, tissue perfusion, permeability, and inflammation in kidney. Improvement of this endothelial dysfunction could be a good approach to treating ischemia-reperfusion-induced renal injury. Cartilage oligomeric matrix protein-angiopoietin-1 (COMP-Ang1) is a variant of native angiogenic factor angiopoietin-1 engineered to have higher activity. We evaluated the protective effect of COMP-Ang1 in an ischemia-reperfusion renal injury model. COMP-Ang1 preserved renal peritubular capillaries after ischemia-reperfusion injury without recruiting pericytes. Pretreatment with COMP-Ang1 attenuated the increase of blood urea nitrogen and serum creatinine levels after ischemia-reperfusion. In addition, the morphological examination indicated less tubular injury in mice pretreated with COMP-Ang1 than in those treated with the vehicle. COMP-Ang1 treatment reduced the increase in the number of Gr-1-positive neutrophils or ER-HR3-positive macrophages infiltrating kidneys, increased phosphorylation of Akt, and preserved renal tissue perfusion flow and microvascular permeability. Furthermore, COMP-Ang1 decreased renal interstitial fibrosis 30 days after the ischemia-reperfusion injury. In conclusion, COMP-Ang1 can be a possible endothelial cell-targeted therapy for preventing ischemia-reperfusion-induced acute kidney injury.
Jung
Yu Jin
YJ
Renal Regeneration Laboratory and Dept. of Internal Medicine, Chonbuk National Univ. Medical School, 634-18 Keum-Am dong, Jeonju 560-180, Korea.
Kim
Duk Hoon
DH
Lee
Ae Sin
AS
Lee
Sik
S
Kang
Kyung Pyo
KP
Lee
Sang Yong
SY
Jang
Kyu Yun
KY
Sung
Mi Jeong
MJ
Park
Sung Kwang
SK
Kim
Won
W
D058186:Acute Kidney Injury / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D000818:Animals; D000950:Antigens, Ly / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D002199:Capillary Permeability / Q000187:drug effects; D042783:Endothelial Cells / Q000473:pathology; D005355:Fibrosis; D015316:Genetic Therapy; D016753:Interleukin-10 / Q000378:metabolism; D007668:Kidney / Q000098:blood supply / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D007677:Kidney Function Tests; D008264:Macrophages / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020556:Neutrophil Infiltration / Q000187:drug effects; D020286:Pericytes / Q000166:cytology; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000627:therapeutic use*; D012079:Renal Circulation / Q000187:drug effects; D015427:Reperfusion Injury / Q000150:complications / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014655:Vascular Resistance / Q000187:drug effects
D000950:Antigens, Ly; C515576:COMP-Ang1 fusion protein; C480309:Ly6G antigen, mouse; D011993:Recombinant Fusion Proteins; D053773:Transforming Growth Factor beta1; D016753:Interleukin-10; D051057:Proto-Oncogene Proteins c-akt