Gene expression profile analysis of 4-phenylbutyrate treatment of IB3-1 bronchial epithelial cell line demonstrates a major influence on heat-shock proteins.
Article Details
- CitationCopy to clipboard
Wright JM, Zeitlin PL, Cebotaru L, Guggino SE, Guggino WB
Gene expression profile analysis of 4-phenylbutyrate treatment of IB3-1 bronchial epithelial cell line demonstrates a major influence on heat-shock proteins.
Physiol Genomics. 2004 Jan 15;16(2):204-11.
- PubMed ID
- 14583596 [ View in PubMed]
- Abstract
Most individuals with cystic fibrosis (CF) carry one or two mutations that result in a maturation defect of the full-length CFTR protein. The DeltaF508 mutation results in a mutant protein that is degraded by the proteosome instead of progressing to the apical membrane where it functions as a cAMP-regulated chloride channel. 4-Phenylbutyrate (PBA) modulates heat-shock protein expression and promotes trafficking of DeltaF508, thus permitting maturation and membrane insertion. The goal of this study was to gain insight into the genetic mechanism of PBA action through a large-scale analysis of gene expression. The Affymetrix genome-spanning U133 microarray set was used to compare mRNA expression levels in untreated IB3-1 cell line cultures with cultures treated with 1 mM PBA for 12 and 24 h. The most notable changes in mRNA levels were transient elevations in heat-shock proteins. The majority of genes downregulated throughout the application period were functionally associated with control of gene expression. Another set of genes increased in expression starting at 24 h, suggesting these are downstream effects of altered gene expression initiated by PBA. More than one-third of the genes in this late expressing set were identified as having potential significance in understanding the pathology of CF. Our results demonstrate the usefulness of gene expression profile analysis in understanding the consequences of PBA treatment and provide insights in how this drug exerts its effect on the trafficking of CFTR.
DrugBank Data that Cites this Article
- Pharmaco-transcriptomics
Drug Drug Groups Gene Gene ID Change Interaction Chromosome Phenylbutyric acid Approved Investigational AARS 16 downregulated 4-phenylbutyric acid results in decreased expression of AARS mRNA 16q22.1 Phenylbutyric acid Approved Investigational AARS 16 upregulated 4-phenylbutyric acid results in increased expression of AARS mRNA 16q22.1 Phenylbutyric acid Approved Investigational AHSA1 10598 upregulated 4-phenylbutyric acid results in increased expression of AHSA1 mRNA 14q24.3 Phenylbutyric acid Approved Investigational AJUBA 84962 downregulated 4-phenylbutyric acid results in decreased expression of AJUBA mRNA 14q11.2 Phenylbutyric acid Approved Investigational AKR1C1 1645 upregulated 4-phenylbutyric acid results in increased expression of AKR1C1 mRNA 10p15.1 Phenylbutyric acid Approved Investigational BCL6 604 upregulated 4-phenylbutyric acid results in increased expression of BCL6 mRNA 3q27.3 Phenylbutyric acid Approved Investigational CARS 833 downregulated 4-phenylbutyric acid results in decreased expression of CARS mRNA 11p15.4 Phenylbutyric acid Approved Investigational CARS 833 upregulated 4-phenylbutyric acid results in increased expression of CARS mRNA 11p15.4 Phenylbutyric acid Approved Investigational CITED2 10370 downregulated 4-phenylbutyric acid results in decreased expression of CITED2 mRNA 6q24.1 Phenylbutyric acid Approved Investigational CLDN1 9076 downregulated 4-phenylbutyric acid results in decreased expression of CLDN1 mRNA 3q28 Phenylbutyric acid Approved Investigational CMSS1 84319 downregulated 4-phenylbutyric acid results in decreased expression of CMSS1 mRNA 3q12.1 Phenylbutyric acid Approved Investigational CNIH4 29097 downregulated 4-phenylbutyric acid results in decreased expression of CNIH4 mRNA 1q42.11 Phenylbutyric acid Approved Investigational CNOT2 4848 downregulated 4-phenylbutyric acid results in decreased expression of CNOT2 mRNA 12q15 Phenylbutyric acid Approved Investigational COL5A1 1289 upregulated 4-phenylbutyric acid results in increased expression of COL5A1 mRNA 9q34.3 Phenylbutyric acid Approved Investigational CSDE1 7812 downregulated 4-phenylbutyric acid results in decreased expression of CSDE1 mRNA 1p13.2 Phenylbutyric acid Approved Investigational CSPG5 10675 upregulated 4-phenylbutyric acid results in increased expression of CSPG5 mRNA 3p21.31 Phenylbutyric acid Approved Investigational DDX55 57696 downregulated 4-phenylbutyric acid results in decreased expression of DDX55 mRNA 12q24.31 Phenylbutyric acid Approved Investigational EEF1E1 9521 downregulated 4-phenylbutyric acid results in decreased expression of EEF1E1 mRNA 6p24.3 Phenylbutyric acid Approved Investigational EFTUD2 9343 downregulated 4-phenylbutyric acid results in decreased expression of EFTUD2 mRNA 17q21.31 Phenylbutyric acid Approved Investigational EHD3 30845 upregulated 4-phenylbutyric acid results in increased expression of EHD3 mRNA 2p23.1 Phenylbutyric acid Approved Investigational FAAH 2166 upregulated 4-phenylbutyric acid results in increased expression of FAAH mRNA 1p33 Phenylbutyric acid Approved Investigational FARSB 10056 downregulated 4-phenylbutyric acid results in decreased expression of FARSB mRNA 2q36.1 Phenylbutyric acid Approved Investigational FBLN1 2192 upregulated 4-phenylbutyric acid results in increased expression of FBLN1 mRNA 22q13.31 Phenylbutyric acid Approved Investigational FGF2 2247 downregulated 4-phenylbutyric acid results in decreased expression of FGF2 mRNA 4q28.1 Phenylbutyric acid Approved Investigational GAS5 60674 downregulated 4-phenylbutyric acid results in decreased expression of GAS5 mRNA 1q25.1 Phenylbutyric acid Approved Investigational GAS6 2621 downregulated 4-phenylbutyric acid results in decreased expression of GAS6 mRNA 13q34 Phenylbutyric acid Approved Investigational GPX3 2878 upregulated 4-phenylbutyric acid results in increased expression of GPX3 mRNA 5q33.1 Phenylbutyric acid Approved Investigational GRB10 2887 upregulated 4-phenylbutyric acid results in increased expression of GRB10 mRNA 7p12.1 Phenylbutyric acid Approved Investigational GSTA4 2941 upregulated 4-phenylbutyric acid results in increased expression of GSTA4 mRNA 6p12.2 Phenylbutyric acid Approved Investigational HLA-E 3133 upregulated 4-phenylbutyric acid results in increased expression of HLA-E mRNA 6p22.1 Phenylbutyric acid Approved Investigational HMGA1 3159 downregulated 4-phenylbutyric acid results in decreased expression of HMGA1 mRNA 6p21.31 Phenylbutyric acid Approved Investigational HNRNPA2B1 3181 downregulated 4-phenylbutyric acid results in decreased expression of HNRNPA2B1 mRNA 7p15.2 Phenylbutyric acid Approved Investigational HNRNPC 3183 downregulated 4-phenylbutyric acid results in decreased expression of HNRNPC mRNA 14q11.2 Phenylbutyric acid Approved Investigational HSPA1A 3303 upregulated 4-phenylbutyric acid results in increased expression of HSPA1A mRNA 6p21.33 Phenylbutyric acid Approved Investigational HSPA2 3306 upregulated 4-phenylbutyric acid results in increased expression of HSPA2 mRNA 14q23.3 Phenylbutyric acid Approved Investigational HSPA4L 22824 upregulated 4-phenylbutyric acid results in increased expression of HSPA4L mRNA 4q28.1 Phenylbutyric acid Approved Investigational HSPH1 10808 upregulated 4-phenylbutyric acid results in increased expression of HSPH1 mRNA 13q12.3 Phenylbutyric acid Approved Investigational ID1 3397 downregulated 4-phenylbutyric acid results in decreased expression of ID1 mRNA 20q11.21 Phenylbutyric acid Approved Investigational IPO11 51194 downregulated 4-phenylbutyric acid results in decreased expression of IPO11 mRNA 5q12.1 Phenylbutyric acid Approved Investigational KMT5B 51111 downregulated 4-phenylbutyric acid results in decreased expression of KMT5B mRNA 11q13.2 Phenylbutyric acid Approved Investigational MAT2A 4144 downregulated 4-phenylbutyric acid results in decreased expression of MAT2A mRNA 2p11.2 Phenylbutyric acid Approved Investigational MIEF1 54471 downregulated 4-phenylbutyric acid results in decreased expression of MIEF1 mRNA 22q13.1 Phenylbutyric acid Approved Investigational MRPS18C 51023 downregulated 4-phenylbutyric acid results in decreased expression of MRPS18C mRNA 4q21.23 Phenylbutyric acid Approved Investigational MRPS22 56945 downregulated 4-phenylbutyric acid results in decreased expression of MRPS22 mRNA 3q23 Phenylbutyric acid Approved Investigational MT1F 4494 upregulated 4-phenylbutyric acid results in increased expression of MT1F mRNA 16q13 Phenylbutyric acid Approved Investigational MT1L 4500 upregulated 4-phenylbutyric acid results in increased expression of MT1L mRNA 16q13 Phenylbutyric acid Approved Investigational NDE1 54820 downregulated 4-phenylbutyric acid results in decreased expression of NDE1 mRNA 16p13.11 Phenylbutyric acid Approved Investigational NIFK 84365 downregulated 4-phenylbutyric acid results in decreased expression of NIFK mRNA 2q14.3 Phenylbutyric acid Approved Investigational NLN 57486 downregulated 4-phenylbutyric acid results in decreased expression of NLN mRNA 5q12.3 Phenylbutyric acid Approved Investigational NOLC1 9221 downregulated 4-phenylbutyric acid results in decreased expression of NOLC1 mRNA 10q24.32 Phenylbutyric acid Approved Investigational NOM1 64434 downregulated 4-phenylbutyric acid results in decreased expression of NOM1 mRNA 7q36.3 Phenylbutyric acid Approved Investigational NR1D2 9975 upregulated 4-phenylbutyric acid results in increased expression of NR1D2 mRNA 3p24.2 Phenylbutyric acid Approved Investigational PAWR 5074 downregulated 4-phenylbutyric acid results in decreased expression of PAWR mRNA 12q21.2 Phenylbutyric acid Approved Investigational PDCD2L 84306 downregulated 4-phenylbutyric acid results in decreased expression of PDCD2L mRNA 19q13.11 Phenylbutyric acid Approved Investigational POLE4 56655 downregulated 4-phenylbutyric acid results in decreased expression of POLE4 mRNA 2p12 Phenylbutyric acid Approved Investigational POLR2A 5430 downregulated 4-phenylbutyric acid results in decreased expression of POLR2A mRNA 17p13.1 Phenylbutyric acid Approved Investigational POLR2A 5430 upregulated 4-phenylbutyric acid results in increased expression of POLR2A mRNA 17p13.1 Phenylbutyric acid Approved Investigational PPIL1 51645 downregulated 4-phenylbutyric acid results in decreased expression of PPIL1 mRNA 6p21.2 Phenylbutyric acid Approved Investigational RBM8A 9939 downregulated 4-phenylbutyric acid results in decreased expression of RBM8A mRNA 1q21.1 Phenylbutyric acid Approved Investigational RPL7A 6130 downregulated 4-phenylbutyric acid results in decreased expression of RPL7A mRNA 9q34.2 Phenylbutyric acid Approved Investigational SARNP 84324 downregulated 4-phenylbutyric acid results in decreased expression of SARNP mRNA 12q13.2 Phenylbutyric acid Approved Investigational SLC22A18 5002 upregulated 4-phenylbutyric acid results in increased expression of SLC22A18 mRNA 11p15.4 Phenylbutyric acid Approved Investigational SLU7 10569 downregulated 4-phenylbutyric acid results in decreased expression of SLU7 mRNA 5q33.3 Phenylbutyric acid Approved Investigational SNX5 27131 downregulated 4-phenylbutyric acid results in decreased expression of SNX5 mRNA 20p11.23 Phenylbutyric acid Approved Investigational SOX4 6659 downregulated 4-phenylbutyric acid results in decreased expression of SOX4 mRNA 6p22.3 Phenylbutyric acid Approved Investigational SRSF10 10772 downregulated 4-phenylbutyric acid results in decreased expression of SRSF10 mRNA 1p36.11 Phenylbutyric acid Approved Investigational SYVN1 84447 downregulated 4-phenylbutyric acid results in decreased expression of SYVN1 mRNA 11q13.1 Phenylbutyric acid Approved Investigational TAX1BP1 8887 downregulated 4-phenylbutyric acid results in decreased expression of TAX1BP1 mRNA 7p15.2 Phenylbutyric acid Approved Investigational TAX1BP3 30851 downregulated 4-phenylbutyric acid results in decreased expression of TAX1BP3 mRNA 17p13.2 Phenylbutyric acid Approved Investigational TIMM50 92609 downregulated 4-phenylbutyric acid results in decreased expression of TIMM50 mRNA 19q13.2 Phenylbutyric acid Approved Investigational TMED5 50999 downregulated 4-phenylbutyric acid results in decreased expression of TMED5 mRNA 1p22.1 Phenylbutyric acid Approved Investigational TMED5 50999 upregulated 4-phenylbutyric acid results in increased expression of TMED5 mRNA 1p22.1 Phenylbutyric acid Approved Investigational TMPO 7112 downregulated 4-phenylbutyric acid results in decreased expression of TMPO mRNA 12q23.1 Phenylbutyric acid Approved Investigational TRA2A 29896 downregulated 4-phenylbutyric acid results in decreased expression of TRA2A mRNA 7p15.3 Phenylbutyric acid Approved Investigational TSC2 7249 upregulated 4-phenylbutyric acid results in increased expression of TSC2 mRNA 16p13.3 Phenylbutyric acid Approved Investigational TSR1 55720 downregulated 4-phenylbutyric acid results in decreased expression of TSR1 mRNA 17p13.3 Phenylbutyric acid Approved Investigational UBA6 55236 downregulated 4-phenylbutyric acid results in decreased expression of UBA6 mRNA 4q13.2 Phenylbutyric acid Approved Investigational UBE2W 55284 downregulated 4-phenylbutyric acid results in decreased expression of UBE2W mRNA 8q21.11 Phenylbutyric acid Approved Investigational UTP4 84916 downregulated 4-phenylbutyric acid results in decreased expression of UTP4 mRNA 16q22.1 Phenylbutyric acid Approved Investigational WDR4 10785 downregulated 4-phenylbutyric acid results in decreased expression of WDR4 mRNA 21q22.3 Phenylbutyric acid Approved Investigational WWTR1 25937 downregulated 4-phenylbutyric acid results in decreased expression of WWTR1 mRNA 3q25.1 Phenylbutyric acid Approved Investigational XPO5 57510 downregulated 4-phenylbutyric acid results in decreased expression of XPO5 mRNA 6p21.1 Phenylbutyric acid Approved Investigational YTHDF2 51441 downregulated 4-phenylbutyric acid results in decreased expression of YTHDF2 mRNA 1p35.3 Phenylbutyric acid Approved Investigational ZBTB2 57621 downregulated 4-phenylbutyric acid results in decreased expression of ZBTB2 mRNA 6q25.1 Phenylbutyric acid Approved Investigational ZNRD1 30834 downregulated 4-phenylbutyric acid results in decreased expression of ZNRD1 mRNA 6p22.1