Date: Monday, June 13, 2016
Session Time: 6:00pm-7:00pm
Presentation Time: 6:00pm-7:00pm
Location: Halls C&D
Background: Clusterin (CLU) is a chaperone-like protein and contributes to the resistance of the kidney to ischemia-reperfusion injury (IRI), however its pathways are not fully understood. This study was designed to investigate CLU-mediating pathways in kidney cells by using bioinformatics analysis.
Materials and Methods: CLU null renal tubular epithelial cells (TECs) expressing human CLU cDNA (TEC-CLUhCLU) or empty vector (TEC-CLU-/-) were exposed to hypoxic condition (1% O2). Transcriptome profiling of these cells under both hypoxia and normoxia was performed using gene expression microarray, and the signaling pathways was identified by using Ingenuity pathway analysis.
Results: Here we showed that ectopic expression of human CLU in CLU null kidney cells enhanced cell survival under hypoxia, and promoted cell growth but inhibited migration under normoxia. Transcriptome profiling showed that under hypoxia, CLU was responsible to down-regulate more numbers of genes compared to TEC-CLU-/- cells and, more cell survival in TEC-CLUhCLU cells compared to TEC-CLU-/- cells was associated with activation of FOXO3- regulates autophagy pathway and with activation of endoplasmic reticulum (ER) stress-unfolded protein response (UPR) (up regulation of FOXO3, IRE1, XBP1).
Under normoxia, the promotion of cell growth or cell cycle progression in TEC-CLUhCLU cells compared to TEC-CLUhCLU cells was related to up-regulation of p21 and GSK3B in PI3K/AKT and up-regulation of FBGFR1 and CREB1 in ERK/MAPK signaling, while the suppressed migration of TEC-CLUhCLU cells was correlated with down-regulation of RHOA and up-regulation of AKT2.
Conclusion: CLU in kidney cells promoted the cell proliferation, restored cell cycle progression and inhibited cell migration under normoxia mainly through PI3K/AKT, and favored cell survival under hypoxia through activated FOXO3 induced autophagy in addition to ER stress/UPR.
CITATION INFORMATION: Dairi G, Guan Q, Collins C, Ong C, Gleave M, Nguan C, Du C. Bioinformatic Analysis of Pathways Mediating Clusterin Functions in Kidney Cells Under Normoxia and Hypoxia. Am J Transplant. 2016;16 (suppl 3).
To cite this abstract in AMA style:Dairi G, Guan Q, Collins C, Ong C, Gleave M, Nguan C, Du C. Bioinformatic Analysis of Pathways Mediating Clusterin Functions in Kidney Cells Under Normoxia and Hypoxia. [abstract]. Am J Transplant. 2016; 16 (suppl 3). https://atcmeetingabstracts.com/abstract/bioinformatic-analysis-of-pathways-mediating-clusterin-functions-in-kidney-cells-under-normoxia-and-hypoxia/. Accessed December 9, 2019.
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