title: Transcriptomic changes in human renal proximal tubular cells revealed under hypoxic conditions by RNA sequencing.
abstract: Chronic hypoxia often occurs among patients with chronic kidney disease (CKD). Renal proximal tubular cells may be the primary target of a hypoxic insult. However, the underlying transcriptional mechanisms remain undefined. In this study, we revealed the global changes in gene expression in HK‑2 human renal proximal tubular cells under hypoxic and normoxic conditions. We analyzed the transcriptome of HK‑2 cells exposed to hypoxia for 24 h using RNA sequencing. A total of 279 differentially expressed genes was examined, as these genes could potentially explain the differences in HK‑2 cells between hypoxic and normoxic conditions. Moreover, 17 genes were validated by qPCR, and the results were highly concordant with the RNA seqencing results. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to better understand the functions of these differentially expressed genes. The upregulated genes appeared to be significantly enriched in the pathyway of extracellular matrix (ECM)-receptor interaction, and in paticular, the pathway of renal cell carcinoma was upregulated under hypoxic conditions. The downregulated genes were enriched in the signaling pathway related to antigen processing and presentation; however, the pathway of glutathione metabolism was downregulated. Our analysis revealed numerous novel transcripts and alternative splicing events. Simultaneously, we also identified a large number of single nucleotide polymorphisms, which will be a rich resource for future marker development. On the whole, our data indicate that transcriptome analysis provides valuable information for a more in depth understanding of the molecular mechanisms in CKD and renal cell carcinoma.
authors.affiliation: Medical School of Southeast University, Nanjing, Jiangsu 210009, P.R. China.
authors.forename: Wenmin
authors.initials: W
authors.lastname: Yu
authors.affiliation: Medical School of Southeast University, Nanjing, Jiangsu 210009, P.R. China.
authors.forename: Yiping
authors.initials: Y
authors.lastname: Li
authors.affiliation: Medical School of Southeast University, Nanjing, Jiangsu 210009, P.R. China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Medical School of Southeast University, Nanjing, Jiangsu 210009, P.R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
authors.affiliation: Medical School of Southeast University, Nanjing, Jiangsu 210009, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.affiliation: Medical School of Southeast University, Nanjing, Jiangsu 210009, P.R. China.
authors.forename: Fengan
authors.initials: F
authors.lastname: Ding
authors.affiliation: Medical School of Southeast University, Nanjing, Jiangsu 210009, P.R. China.
authors.forename: Xiaoyi
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Medical School of Southeast University, Nanjing, Jiangsu 210009, P.R. China.
authors.forename: Zhengyuan
authors.initials: Z
authors.lastname: Cheng
authors.affiliation: Medical School of Southeast University, Nanjing, Jiangsu 210009, P.R. China.
authors.forename: Pingsheng
authors.initials: P
authors.lastname: Chen
authors.affiliation: Medical School of Southeast University, Nanjing, Jiangsu 210009, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Dou
mesh_terms: D017398:Alternative Splicing / Q000235:genetics; D015153:Blotting, Western; D015687:Cell Hypoxia; D002460:Cell Line; D020869:Gene Expression Profiling / Q000379:methods*; D063990:Gene Ontology; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide; D051436:Renal Insufficiency, Chronic / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017423:Sequence Analysis, RNA / Q000379:methods*; D015398:Signal Transduction / Q000235:genetics; D059467:Transcriptome
chemical_list: C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit