Down-regulation of GRP78 alleviates lipopolysaccharide-induced acute kidney injury. 2018

Jinlong Teng, and Mingjun Liu, and Yuan Su, and Kun Li, and Na Sui, and Shibo Wang, and Liandi Li, and Yunbo Sun, and Yongbin Wang
Department of Critical Care Medicine, The Affiliated Hospital of Qingdao University, Qingdao, China.

OBJECTIVE Acute kidney injury (AKI) is accompanied with life-threatening sepsis. It is necessary to develop effective therapy agent or strategy for treating AKI. LPS is a primary pathogenic factor that induces sepsis. Glucose-regulated protein 78 (GRP78) is closely related to cell injuries. The objective of this study was to examine the role of GRP78 in LPS-induced AKI. METHODS Cell counting kit-8 (CCK-8) assay and flow cytometry (FCM) were respectively performed to assess the cell viability and apoptosis. Available commercial kits were used to detect the reactive oxygen species (ROS) contents and the activity of oxidative indicators. The expressions of the relevant factors were determined by real-time PCR (RT-PCR) and Western blot. RESULTS The results showed that the expression of GRP78 was apparently increased by LPS treatment, and that the down-regulation of GRP78 by small RNA interference improved the proliferation ability of renal cells in comparison to LPS group. The LPS-induced immune response and oxidative stress was alleviated by the depletion of GRP78. Moreover, the LPS-induced apoptosis was reduced in the GRP78 group by regulating the expression of mitochondrial apoptosis (Bcl-2, Bax) and endoplasmic reticulum (ER) stress (CHOP, caspase-12)-associated proteins. In addition, the protective role of GRP78 reduction was partly related to the balance of NF-κB/IκB. CONCLUSIONS Down-regulation of GRP78 attenuated LPS-induced AKI through inhibiting immune response/oxidative stress-associated apoptosis.

UI MeSH Term Description Entries
D007684 Kidney Tubules Long convoluted tubules in the nephrons. They collect filtrate from blood passing through the KIDNEY GLOMERULUS and process this filtrate into URINE. Each renal tubule consists of a BOWMAN CAPSULE; PROXIMAL KIDNEY TUBULE; LOOP OF HENLE; DISTAL KIDNEY TUBULE; and KIDNEY COLLECTING DUCT leading to the central cavity of the kidney (KIDNEY PELVIS) that connects to the URETER. Kidney Tubule,Tubule, Kidney,Tubules, Kidney
D008070 Lipopolysaccharides Lipid-containing polysaccharides which are endotoxins and important group-specific antigens. They are often derived from the cell wall of gram-negative bacteria and induce immunoglobulin secretion. The lipopolysaccharide molecule consists of three parts: LIPID A, core polysaccharide, and O-specific chains (O ANTIGENS). When derived from Escherichia coli, lipopolysaccharides serve as polyclonal B-cell mitogens commonly used in laboratory immunology. (From Dorland, 28th ed) Lipopolysaccharide,Lipoglycans
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D002470 Cell Survival The span of viability of a cell characterized by the capacity to perform certain functions such as metabolism, growth, reproduction, some form of responsiveness, and adaptability. Cell Viability,Cell Viabilities,Survival, Cell,Viabilities, Cell,Viability, Cell
D004847 Epithelial Cells Cells that line the inner and outer surfaces of the body by forming cellular layers (EPITHELIUM) or masses. Epithelial cells lining the SKIN; the MOUTH; the NOSE; and the ANAL CANAL derive from ectoderm; those lining the RESPIRATORY SYSTEM and the DIGESTIVE SYSTEM derive from endoderm; others (CARDIOVASCULAR SYSTEM and LYMPHATIC SYSTEM) derive from mesoderm. Epithelial cells can be classified mainly by cell shape and function into squamous, glandular and transitional epithelial cells. Adenomatous Epithelial Cells,Columnar Glandular Epithelial Cells,Cuboidal Glandular Epithelial Cells,Glandular Epithelial Cells,Squamous Cells,Squamous Epithelial Cells,Transitional Epithelial Cells,Adenomatous Epithelial Cell,Cell, Adenomatous Epithelial,Cell, Epithelial,Cell, Glandular Epithelial,Cell, Squamous,Cell, Squamous Epithelial,Cell, Transitional Epithelial,Cells, Adenomatous Epithelial,Cells, Epithelial,Cells, Glandular Epithelial,Cells, Squamous,Cells, Squamous Epithelial,Cells, Transitional Epithelial,Epithelial Cell,Epithelial Cell, Adenomatous,Epithelial Cell, Glandular,Epithelial Cell, Squamous,Epithelial Cell, Transitional,Epithelial Cells, Adenomatous,Epithelial Cells, Glandular,Epithelial Cells, Squamous,Epithelial Cells, Transitional,Glandular Epithelial Cell,Squamous Cell,Squamous Epithelial Cell,Transitional Epithelial Cell
D006360 Heat-Shock Proteins Proteins which are synthesized in eukaryotic organisms and bacteria in response to hyperthermia and other environmental stresses. They increase thermal tolerance and perform functions essential to cell survival under these conditions. Stress Protein,Stress Proteins,Heat-Shock Protein,Heat Shock Protein,Heat Shock Proteins,Protein, Stress
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000091342 Endoplasmic Reticulum Chaperone BiP An ENDOPLASMIC RETICULUM specific chaperone of the HSP70 family. They are involved in folding and oligomerization of secreted and membrane proteins and ENDOPLASMIC RETICULUM STRESS related UNFOLDED PROTEIN RESPONSE. Binding-immunoglobulin Protein Molecular Chaperone,Glucose Regulated Protein 78 kDa,Grp78,HSPA5 Protein,Heat-Shock Protein 5,Molecular Chaperone BiP,Molecular Chaperone GRP78,BiP, Molecular Chaperone,Binding immunoglobulin Protein Molecular Chaperone,GRP78, Molecular Chaperone,Heat Shock Protein 5,Protein, HSPA5
D014162 Transfection The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES. Transfections
D014409 Tumor Necrosis Factor-alpha Serum glycoprotein produced by activated MACROPHAGES and other mammalian MONONUCLEAR LEUKOCYTES. It has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. Also known as TNF-alpha, it is only 30% homologous to TNF-beta (LYMPHOTOXIN), but they share TNF RECEPTORS. Cachectin,TNF-alpha,Tumor Necrosis Factor Ligand Superfamily Member 2,Cachectin-Tumor Necrosis Factor,TNF Superfamily, Member 2,TNFalpha,Tumor Necrosis Factor,Cachectin Tumor Necrosis Factor,Tumor Necrosis Factor alpha

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