title: Progranulin protects against renal ischemia/reperfusion injury in mice.
abstract: Progranulin (PGRN), an autocrine growth factor, has multiple physiological functions and is widely involved in the pathogenesis of many types of diseases. The pivotal anti-inflammatory function of PGRN in rheumatoid arthritis encouraged us to examine the role of PGRN in acute kidney injury (AKI). We found that levels of PGRN were significantly reduced in the kidney in a mouse model of renal ischemia/reperfusion injury. We also observed that PGRN deficiency (Grn(-/-) mice) significantly aggravated renal injury as evidenced by higher serum creatinine, more severe morphological injury, increased tubular epithelial cell death, and tubulointerstitial neutrophil and macrophage infiltration versus wild-type mice. In vitro, we found that recombinant human PGRN attenuated hypoxia-induced inflammatory actions and apoptosis in proximal tubule epithelial cells, at least in part associated with a nucleotide-binding oligomerization domain containing 2 (NOD2)-mediated immune response. Importantly, pretreatment with or delayed administration of recombinant human PGRN protected against or promoted recovery from renal ischemia/reperfusion injury in wild-type and Grn(-/-) mice. Similar protective effects were also found in cisplatin-induced AKI. Thus, our findings provide a better understanding of the biological activities of PGRN in the kidney and suggest that PGRN may be an innovative therapeutic strategy for treating patients with AKI.
authors.affiliation: Department of Pharmacology, Shandong University School of Medicine, Jinan, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Zhou
authors.affiliation: Department of Pathogenic Biology, Shandong University School of Medicine, Jinan, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Tang
authors.affiliation: Department of Pharmacology, Shandong University School of Medicine, Jinan, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Fu
authors.affiliation: Department of Pathogenic Biology, Shandong University School of Medicine, Jinan, China.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Pharmacology, Shandong University School of Medicine, Jinan, China.
authors.forename: Ziying
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Biochemistry and Molecular Biology, Shandong University School of Medicine, Jinan, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Biochemistry and Molecular Biology, Shandong University School of Medicine, Jinan, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Liu
authors.affiliation: Institute of Pharmaceutical Analysis, School of Pharmacy, Shandong University, Jinan, China.
authors.forename: Xinying
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Pharmacology, Shandong University School of Medicine, Jinan, China.
authors.forename: Xinbing
authors.initials: X
authors.lastname: Wei
authors.affiliation: Department of Pharmacology, Shandong University School of Medicine, Jinan, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Pathogenic Biology, Shandong University School of Medicine, Jinan, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Pharmacology, Shandong University School of Medicine, Jinan, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Geng
authors.affiliation: Department of Nephrology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Chun
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Nephrology, Provincial Hospital Affiliated to Shandong University, Jinan, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wan
authors.affiliation: Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, Richmond, VA, USA.
authors.forename: Ningjun
authors.initials: N
authors.lastname: Li
authors.affiliation: 1] Department of Pharmacology, Shandong University School of Medicine, Jinan, China [2] Institute of Nephrology, Shandong University, Jinan, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Yi
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D002945:Cisplatin; D004847:Epithelial Cells / Q000502:physiology; D000077155:Granulins; D006801:Humans; D000860:Hypoxia / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism*; D007687:Kidney Tubules, Proximal / Q000166:cytology; D008297:Male; D051379:Mice; D053473:Nod2 Signaling Adaptor Protein / Q000378:metabolism; D000077153:Progranulins; D015427:Reperfusion Injury / Q000378:metabolism*
chemical_list: D000077155:Granulins; C120204:Grn protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D053473:Nod2 Signaling Adaptor Protein; C495945:Nod2 protein, mouse; D000077153:Progranulins; D002945:Cisplatin