title: Long non-coding RNA PVT1 promote LPS-induced septic acute kidney injury by regulating TNFα and JNK/NF-κB pathways in HK-2 cells.
abstract: This study aimed to investigate the effect and underlying mechanism of long non-coding RNA plasmacytoma variant translocation 1 (PVT1) in lipopolysaccharide (LPS)-induced inflammation injury in HK-2 cells. We established LPS-induced septic acute kidney injury (AKI) model in HK-2 cells. LPS-induced HK-2 cells were transfected with pc-PVT1, pc-NC, si-PVT1 or si-NC. Cell viability and apoptosis rate were detected by MTT assay and Annexin V-FITC/PI Apoptosis Detection kit, respectively. The relationships of PVT1 and inflammatory factors were evaluated by RNA Immunoprecipitation (RIP) assay. The levels of inflammatory factors, apoptosis-related proteins and the expressions of proteins related to c-Jun N-terminal kinase (JNK) and nuclear factor-κB (NF-κB) signaling pathway were detected by ELISA or Western blotting. Compared with cells with pc-NC, cell viability was remarkably decreased and cell apoptosis rate was increased in LPS-induced cells with pc-PVT1 (p<0.05). The levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and IL-1β were significantly increased in LPS-induced cells with pc-PVT1 compared with cells with pc-NC (p<0.05). All these changes were reversed in LPS-induced cells with si-PVT1 and si-NC (p<0.05). RTP assay revealed that PVT1 could bind to TNF-α. Furthermore, down-regulated PVT1 remarkably reduced the expressions of p-JNK and p-c-Jun, p-IκBα and p-p65 (p<0.05); while increased expressions of these proteins and inflammatory factors induced by up-regulated PVT1 were reversed by JNK or NF-κB inhibitors. PVT1 may promote inflammatory response by binding to TNF-α and inhibiting JNK/NF-κB signaling pathway in LPS-induced septic AKI cells.
authors.affiliation: Department of Intensive Care Unit, The Affiliated Tumor Hospital of Harbin Medical University, Harbin, Heilongjiang 150081, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Huang
authors.affiliation: Department of Intensive Care Unit, The Affiliated Tumor Hospital of Harbin Medical University, Harbin, Heilongjiang 150081, China.
authors.forename: Xiuwen
authors.initials: X
authors.lastname: Lan
authors.affiliation: Department of Intensive Care Unit, The Affiliated Tumor Hospital of Harbin Medical University, Harbin, Heilongjiang 150081, China.
authors.forename: Xueting
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Intensive Care Unit, The Affiliated Tumor Hospital of Harbin Medical University, Harbin, Heilongjiang 150081, China.
authors.forename: Dawei
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Intensive Care Unit, The Affiliated Tumor Hospital of Harbin Medical University, Harbin, Heilongjiang 150081, China.
authors.forename: Yinghao
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Intensive Care Unit, The Affiliated Tumor Hospital of Harbin Medical University, Harbin, Heilongjiang 150081, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Intensive Care Unit, The Affiliated Tumor Hospital of Harbin Medical University, Harbin, Heilongjiang 150081, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Gao
authors.affiliation: Department of Intensive Care Unit, The Affiliated Tumor Hospital of Harbin Medical University, Harbin, Heilongjiang 150081, China. Electronic address: shuiqinghu11@126.com.
authors.forename: Kaijiang
authors.initials: K
authors.lastname: Yu
mesh_terms: D058186:Acute Kidney Injury / Q000139:chemically induced / Q000235:genetics / Q000276:immunology*; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000502:physiology*; D006801:Humans; D056747:Immunomodulation / Q000235:genetics; D007249:Inflammation; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007668:Kidney / Q000473:pathology*; D008070:Lipopolysaccharides / Q000276:immunology; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D062085:RNA, Long Noncoding / Q000235:genetics* / Q000276:immunology; D034741:RNA, Small Interfering / Q000235:genetics; D018805:Sepsis / Q000139:chemically induced / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; C521123:PVT1 long-non-coding RNA, human; D062085:RNA, Long Noncoding; D034741:RNA, Small Interfering; D014409:Tumor Necrosis Factor-alpha; D048670:MAP Kinase Kinase 4
keywords: Inflammatory response; JNK/NF-κB signaling pathway; Plasmacytoma variant translocation 1; Septic acute kidney injury