title: RANTES mediates kidney ischemia reperfusion injury through a possible role of HIF-1α and LncRNA PRINS.
abstract: RANTES (Regulated on activation, normal T-cell expressed and secreted), recruits circulating leukocytes and augments inflammatory responses in many clinical conditions. Inflammatory responses in ischemia-reperfusion injury (IRI) significantly affect the unfavorable outcomes of acute kidney injury (AKI), and that infiltrating immune cells are important mediators of AKI. However, the significance of RANTES in AKI and whether hypoxia-induced LncRNAs are involved in the regulatory process of AKI are not known. Here we show that, in the kidney IRI mice model, significant RANTES expression was observed in renal tubular cells of wild type mice. RANTES deficient (RANTES(-/-)) mice showed better renal function by reducing the acute tubular necrosis, serum creatinine levels, infiltration of inflammatory cells and cytokine expressions compared to wild type. In vitro, we found that RANTES expression was regulated by NF-κB. Further, renal tubular cells showed deregulated LncRNA expression under hypoxia. Among HIF-1α dependent LncRNAs, PRINS (Psoriasis susceptibility-related RNA Gene Induced by Stress) was significantly up regulated in hypoxic conditions and had specific interaction with RANTES as confirmed through reporter assay. These observations show first evidence for RANTES produced by renal tubular cells act as a key chemokine in AKI and HIF-1α regulated LncRNA-PRINS might be involved in RANTES production.
authors.affiliation: Graduate Institute of Clinical Medical Science, China Medical University, Taiwan.|Division of Nephrology, Department of Internal Medicine, Taichung Veterans General Hospital, Taiwan.
authors.forename: Tung-Min
authors.initials: TM
authors.lastname: Yu
authors.affiliation: Graduate Institute of Clinical Medical Science, China Medical University, Taiwan.
authors.forename: Kalaiselvi
authors.initials: K
authors.lastname: Palanisamy
authors.affiliation: Graduate Institute of Clinical Medical Science, China Medical University, Taiwan.|Department of Pediatric Dentistry, China Medical University Hospital, Taiwan.|School of Dentistry, China Medical University, Taiwan.
authors.forename: Kuo-Ting
authors.initials: KT
authors.lastname: Sun
authors.affiliation: Department of Anesthesiology, Chang Gung Memorial Hospital, Taiwan.|Graduate Institute of Clinical Medical Sciences, Chang Gung University, Taiwan.
authors.forename: Yuan-Ji
authors.initials: YJ
authors.lastname: Day
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Taichung Veterans General Hospital, Taiwan.
authors.forename: Kuo-Hsiung
authors.initials: KH
authors.lastname: Shu
authors.affiliation: Graduate Institute of Clinical Medical Science, China Medical University, Taiwan.|Division of Nephrology, China Medical University Hospital, Taiwan.
authors.forename: I-Kuan
authors.initials: IK
authors.lastname: Wang
authors.affiliation: Graduate Institute of Immunology, China Medical University, Taichung, Taiwan.|Center for Neuropsychiatry, Department of Neurology, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Woei-Cherng
authors.initials: WC
authors.lastname: Shyu
authors.affiliation: Thalassemia Research Institute, The First Affiliated Hospital, Guangxi Medical University, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Chen
authors.affiliation: Department of Anatomy and Cell Biology, National Taiwan University, Taipei, Taiwan.
authors.forename: Yuh-Lien
authors.initials: YL
authors.lastname: Chen
authors.affiliation: Graduate Institute of Clinical Medical Science, China Medical University, Taiwan.|Department of Anesthesiology, China Medical University Hospital, Taiwan.
authors.forename: Chi-Yuan
authors.initials: CY
authors.lastname: Li
mesh_terms: D000818:Animals; D015687:Cell Hypoxia; D018946:Chemokine CCL5 / Q000502:physiology*; D015870:Gene Expression; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000502:physiology*; D007511:Ischemia; D007668:Kidney / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016328:NF-kappa B / Q000378:metabolism; D020556:Neutrophil Infiltration; D062085:RNA, Long Noncoding / Q000235:genetics* / Q000378:metabolism; D015427:Reperfusion Injury / Q000378:metabolism*
chemical_list: C503460:Ccl5 protein, mouse; D018946:Chemokine CCL5; C497443:Hif1a protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D016328:NF-kappa B; D062085:RNA, Long Noncoding; C000612840:long non-coding RNA PRINS, mouse