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Titolo:
Time course of LPS- induced gene expression in a mouse model of genitourinary inflammation
Autore:
Saban, MR; Hellmich, H; Nguyen, NB; Winston, J; Hammond, TG; Saban, R;
Indirizzi:
Univ Oklahoma, Hlth Sci Ctr, Coll Med, Dept Physiol, Oklahoma City, OK 73190 USA Univ Oklahoma Oklahoma City OK USA 73190 iol, Oklahoma City, OK 73190 USA Univ Texas, Med Branch, Dept Internal Med, Galveston, TX 77555 USA Univ Texas Galveston TX USA 77555 t Internal Med, Galveston, TX 77555 USA Tulane Univ, Med Ctr, Tulane Environm Astrobiol Ctr, New Orleans, LA 70112USA Tulane Univ New Orleans LA USA 70112 robiol Ctr, New Orleans, LA 70112USA Tulane Univ, Med Ctr, Nephrol Sect, New Orleans, LA 70112 USA Tulane UnivNew Orleans LA USA 70112 hrol Sect, New Orleans, LA 70112 USA Vet Affairs Med Ctr, New Orleans, LA 70112 USA Vet Affairs Med Ctr New Orleans LA USA 70112 r, New Orleans, LA 70112 USA
Titolo Testata:
PHYSIOLOGICAL GENOMICS
fascicolo: 3, volume: 5, anno: 2001,
pagine: 147 - 160
SICI:
1094-8341(20010402)5:3<147:TCOLIG>2.0.ZU;2-9
Fonte:
ISI
Lingua:
ENG
Soggetto:
NERVE GROWTH-FACTOR; RAT URINARY-BLADDER; INTERSTITIAL CYSTITIS; DNA MICROARRAYS; SUBSTANCE-P; CELL-LINE; BINDING-PROTEIN; MESSENGER-RNA; ENDOTOXIN; RECEPTOR;
Keywords:
gene array; mouse model of disease; urinary bladder inflammation; interstitial cystitis;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
48
Recensione:
Indirizzi per estratti:
Indirizzo: Saban, R Univ Oklahoma, Hlth Sci Ctr, Coll Med, Dept Physiol, 940 SL YoungBlvd,Rm 605, Oklahoma City, OK 73190 USA Univ Oklahoma 940 SL Young Blvd,Rm 605 Oklahoma City OK USA 73190
Citazione:
M.R. Saban et al., "Time course of LPS- induced gene expression in a mouse model of genitourinary inflammation", PHYSIOL GEN, 5(3), 2001, pp. 147-160

Abstract

In this study, self-organizing map (SOM) gene cluster techniques are applied to the analysis of cDNA microarray analysis of gene expression changes occurring in the early stages of genitourinary inflammation. We determined the time course of lipopolysaccharide (LPS) induced gene expression in experimental cystitis. Mice were euthanized 0.5, 1, 4, and 24 h after LPS instillation into the urinary bladder, and gene expression was determined using four replicate Atlas mouse cDNA expression arrays containing 588 known genesat each time point. SOM gene cluster analysis, performed without preconditions, identified functionally significant gene clusters based on the kinetics of change in gene expression. Genes were classified as follows: 1) expressed at time 0; 2) early genes (peak expression between 0.5 and 1 h); and 3) late genes (peak expression between 4 and 24 h). One gene cluster maintained a constant level of expression during the entire time period studied. In contrast, LPS treatment downregulated the expression of some genes expressed at time 0, in a cluster including transcription factors, protooncogenes, apoptosis-related proteins (cysteine protease), intracellular kinases, and growth factors. Gene upregulation in response to LPS was observed as early as 0.5 h in a cluster including the interleukin-6 (IL-6) receptor, alpha-and beta -nerve growth factor (alpha- and beta -NGF), vascular endothelialgrowth factor receptor-1 (VEGF R1), C-C chemokine receptor, and P-selectin. Another tight cluster of genes with marked expression at 1 h after LPS and insignificant expression at all other time points studied included the protooncogenes c-Fos, Fos-B, Fra-2, Jun-B, Jun-D, and Egr-1. Almost all interleukin genes were upregulated as early as 1 h after stimulation with LPS. Nuclear factor-kappaB (NF-kappaB) pathway genes collected in a single cluster with a peak expression 4 h after LPS stimulation. In contrast, most of the interleukin receptors and chemokine receptors presented a late peak of expression 24 h after LPS coinciding with the peak of neutrophil infiltrationinto the bladder wall. Selected cDNA microarray observations were confirmed by RNase protection assay. In conclusion, the cDNA array experimental approach provided a global profile of gene expression changes in bladder tissue after stimulation with LPS. SOM techniques identified functionally significant gene clusters, providing a powerful technical basis for future analysis of mechanisms of bladder inflammation.

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Documento generato il 04/04/20 alle ore 01:28:04