title: Recruitment and subsequent proliferation of bone marrow-derived cells in the postischemic kidney are important to the progression of fibrosis.
abstract: Acute kidney injury (AKI) is an independent risk factor of the development of chronic kidney disease. Kidney fibrosis is a typical feature of chronic kidney disease and is characterized as an expansion of the interstitium due to increases in extracellular matrix molecules and interstitial cells caused by accumulations of extrarenal cells and by the proliferation or differentiation of intrarenal cells. However, the role of bone marrow-derived cells (BMDCs) in AKI-induced kidney fibrosis remains to be defined. Here, we investigated the role of BMDCs in kidney fibrosis after ischemia-reperfusion injury (IRI)-induced AKI in green fluorescent protein (GFP)-expressing bone marrow chimeric mice. IRI resulted in severe fibrotic changes in kidney tissues and dramatically increased interstitial cell numbers. Furthermore, GFP-expressing BMDCs accounted for >80% of interstitial cells in fibrotic kidneys. Interstitial GFP-expressing cells expressed α-smooth muscle actin (a myofibroblast marker), fibroblast-specific protein-1 (a fibroblast marker), collagen type III, and F4/80 (a macrophage marker). Over 20% of interstitial cells were bromodeoxyuridine-incorporating (proliferating) cells, and of these, 80% cells were GFP-expressing BMDCs. Daily treatment of IRI mice with apocynin (a NADPH oxidase inhibitor that functions as an antioxidant) from the day after surgery until euthanization slightly inhibited these changes with a small reduction of fibrosis. Taken together, our findings show that BMDCs make a major contribution to IRI-induced fibrosis due to their infiltration, subsequent differentiation, and proliferation in injured kidneys, suggesting that BMDCs be considered an important target for the treatment of kidney fibrosis.
authors.affiliation: Department of Anatomy and BK21 Plus Biomedical Convergence Program, Kyungpook National University School of Medicine, Daegu, Republic of Korea; Cardiovascular Research Institute, Kyungpook National University School of Medicine, Daegu, Republic of Korea; and.
authors.forename: Hee-Seong
authors.initials: HS
authors.lastname: Jang
authors.affiliation: Department of Molecular Medicine, Keimyung University School of Medicine, Daegu, Republic of Korea.
authors.forename: Jee In
authors.initials: JI
authors.lastname: Kim
authors.affiliation: Department of Anatomy and BK21 Plus Biomedical Convergence Program, Kyungpook National University School of Medicine, Daegu, Republic of Korea;
authors.forename: Sang Jun
authors.initials: SJ
authors.lastname: Han
authors.affiliation: Department of Anatomy and BK21 Plus Biomedical Convergence Program, Kyungpook National University School of Medicine, Daegu, Republic of Korea; Cardiovascular Research Institute, Kyungpook National University School of Medicine, Daegu, Republic of Korea; and kmpark@knu.ac.kr.
authors.forename: Kwon Moo
authors.initials: KM
authors.lastname: Park
mesh_terms: D000098:Acetophenones / Q000494:pharmacology; D058186:Acute Kidney Injury / Q000209:etiology* / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D001854:Bone Marrow Cells / Q000473:pathology*; D016026:Bone Marrow Transplantation; D049109:Cell Proliferation; D002678:Chimera; D003094:Collagen / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D005355:Fibrosis; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D007668:Kidney / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015427:Reperfusion Injury / Q000150:complications*
chemical_list: D000098:Acetophenones; D049452:Green Fluorescent Proteins; D003094:Collagen; C056165:acetovanillone
keywords: bone marrow-derived cell; fibroblast; fibrosis; ischemia; macrophage