title: Progranulin protects against endotoxin-induced acute kidney injury by downregulating renal cell death and inflammatory responses in mice.
abstract: Progranulin (PGRN), a pluripotent secreted growth factor, is involved in various physiologic and disease processes. However, the role of PGRN in endotoxin-induced septic acute kidney injury (AKI) remains unknown. The objective of this study is to investigate the protective effects of PGRN on an endotoxin-induced AKI mouse model by using PGRN-deficient mice and recombinant PGRN (rPGRN) pretreatment. PGRN levels were increased in kidneys of wild-type (WT) mice at 6 and 24h after lipopolysaccharide (LPS) injection. Renal function detection, hematoxylin and eosin staining, immunohistochemical staining, ELISA and in situ terminal deoxynucleotidyl transferase-mediated uridine triphosphate nick-end labeling were used to reveal tissue injury, inflammatory cell infiltration, production of inflammatory mediators and cell death in mouse kidneys after LPS injection. PGRN deficiency resulted in severe kidney injury and increased apoptotic death, inflammatory cell infiltration, production of pro-inflammatory mediators and the expression and nucleus-to-cytoplasmic translocation of HMGB1 in the kidney. In addition, rPGRN administration before LPS treatment ameliorated the endotoxin-induced AKI in WT mice. PGRN may be a novel biologic agent with therapeutic potential for endotoxin-induced septic AKI possibly by inhibiting LPS-induced renal cell death and inflammatory responses in mice.
authors.affiliation: Department of Pathogenic Biology, Shandong University School of Medicine, Jinan, Shandong, PR China.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Pathogenic Biology, Shandong University School of Medicine, Jinan, Shandong, PR China.
authors.forename: Linfeng
authors.initials: L
authors.lastname: Gou
authors.affiliation: Department of Pharmacology, Shandong University School of Medicine, Jinan, Shandong, PR China.
authors.forename: Meng
authors.initials: M
authors.lastname: Zhou
authors.affiliation: Department of Biochemistry and Molecular Biology, Shandong University School of Medicine, Jinan, Shandong, PR China.
authors.forename: Fusheng
authors.initials: F
authors.lastname: Yang
authors.affiliation: Department of Pathogenic Biology, Shandong University School of Medicine, Jinan, Shandong, PR China.
authors.forename: Yihan
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Pathogenic Biology, Shandong University School of Medicine, Jinan, Shandong, PR China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Feng
authors.affiliation: Department of Pathogenic Biology, Shandong University School of Medicine, Jinan, Shandong, PR China.
authors.forename: Peikun
authors.initials: P
authors.lastname: Shi
authors.affiliation: Department of Pathogenic Biology, Shandong University School of Medicine, Jinan, Shandong, PR China.
authors.forename: Armin
authors.initials: A
authors.lastname: Ghavamian
authors.affiliation: Department of Pathogenic Biology, Shandong University School of Medicine, Jinan, Shandong, PR China.
authors.forename: Weiming
authors.initials: W
authors.lastname: Zhao
authors.affiliation: Department of Hematology, Qilu Hospital of Shandong University, Jinan, Shandong, PR China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Department of Biochemistry and Molecular Biology, Shandong University School of Medicine, Jinan, Shandong, PR China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Pharmacology, Shandong University School of Medicine, Jinan, Shandong, PR China.
authors.forename: Fan
authors.initials: F
authors.lastname: Yi
authors.affiliation: Department of Nephrology, Qilu Hospital of Shandong University, Jinan, Shandong, PR China. Electronic address: guangyi.liu3@gmail.com.
authors.forename: Guangyi
authors.initials: G
authors.lastname: Liu
authors.affiliation: Department of Pathogenic Biology, Shandong University School of Medicine, Jinan, Shandong, PR China. Electronic address: weitang@sdu.edu.cn.
authors.forename: Wei
authors.initials: W
authors.lastname: Tang
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced / Q000188:drug therapy*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D004195:Disease Models, Animal; D000077155:Granulins; D024243:HMGB1 Protein / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000188:drug therapy*; D018836:Inflammation Mediators / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D008070:Lipopolysaccharides / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000077153:Progranulins; D011994:Recombinant Proteins / Q000235:genetics / Q000627:therapeutic use*
chemical_list: D000077155:Granulins; C120204:Grn protein, mouse; D024243:HMGB1 Protein; C582808:HMGB1 protein, mouse; D018836:Inflammation Mediators; D036341:Intercellular Signaling Peptides and Proteins; D008070:Lipopolysaccharides; D000077153:Progranulins; D011994:Recombinant Proteins
keywords: Acute kidney injury; Apoptosis; Endotoxemia; Inflammation; Progranulin