The inflammatory and normal transcriptome of mouse bladder detrusor and mucosa

Marcia R. Saban, Helen Hellmich, Mary Turner, Ngoc Bich Nguyen, Rajanikanth Vadigepalli, David W. Dyer, Robert E. Hurst, Michael Centola, Ricardo Saban

Research output: Contribution to journalArticle

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Abstract

Background: An organ such as the bladder consists of complex, interacting set of tissues and cells. Inflammation has been implicated in every major disease of the bladder, including cancer, interstitial cystitis, and infection. However, scanty is the information about individual detrusor and urothelium transcriptomes in response to inflammation. Here, we used suppression subtractive hybridizations (SSH) to determine bladder tissue- and disease-specific genes and transcriptional regulatory elements (TRE)s. Unique TREs and genes were assembled into putative networks. Results: It was found that the control bladder mucosa presented regulatory elements driving genes such as myosin light chain phosphatase and calponin I that influence the smooth muscle phenotype. In the control detrusor network the Pax-3 TRE was significantly over-represented. During development, the Pax-3 transcription factor (TF) maintains progenitor cells in an undifferentiated state whereas, during inflammation, Pax-3 was suppressed and genes involved in neuronal development (synapsin I) were up-regulated. Therefore, during inflammation, an increased maturation of neural progenitor cells in the muscle may underlie detrusor instability. NF-κB was specifically over-represented in the inflamed mucosa regulatory network. When the inflamed detrusor was compared to control, two major pathways were found, one encoding synapsin I, a neuron-specific phosphoprotein, and the other an important apoptotic protein, siva. In response to LPS-induced inflammation, the liver X receptor was over-represented in both mucosa and detrusor regulatory networks confirming a role for this nuclear receptor in LPS-induced gene expression. Conclusion: A new approach for understanding bladder muscle-urothelium interaction was developed by assembling SSH, real time PCR, and TRE analysis results into regulatory networks. Interestingly, some of the TREs and their downstream transcripts originally involved in organogenesis and oncogenesis were also activated during inflammation. The latter represents an additional link between inflammation and cancer. The regulatory networks represent key targets for development of novel drugs targeting bladder diseases.

Original languageEnglish (US)
JournalBMC Physiology
Volume6
DOIs
StatePublished - Jan 18 2006

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Transcriptome
Mucous Membrane
Urinary Bladder
Inflammation
Transcriptional Regulatory Elements
Urinary Bladder Diseases
Synapsins
Urothelium
Genes
Paired Box Transcription Factors
Stem Cells
Myosin-Light-Chain Phosphatase
Interstitial Cystitis
Muscles
Organogenesis
Phosphoproteins
Drug Delivery Systems
Cytoplasmic and Nuclear Receptors
Urinary Bladder Neoplasms
Smooth Muscle

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Saban, M. R., Hellmich, H., Turner, M., Nguyen, N. B., Vadigepalli, R., Dyer, D. W., ... Saban, R. (2006). The inflammatory and normal transcriptome of mouse bladder detrusor and mucosa. BMC Physiology, 6. https://doi.org/10.1186/1472-6793-6-1

The inflammatory and normal transcriptome of mouse bladder detrusor and mucosa. / Saban, Marcia R.; Hellmich, Helen; Turner, Mary; Nguyen, Ngoc Bich; Vadigepalli, Rajanikanth; Dyer, David W.; Hurst, Robert E.; Centola, Michael; Saban, Ricardo.

In: BMC Physiology, Vol. 6, 18.01.2006.

Research output: Contribution to journalArticle

Saban, MR, Hellmich, H, Turner, M, Nguyen, NB, Vadigepalli, R, Dyer, DW, Hurst, RE, Centola, M & Saban, R 2006, 'The inflammatory and normal transcriptome of mouse bladder detrusor and mucosa', BMC Physiology, vol. 6. https://doi.org/10.1186/1472-6793-6-1
Saban, Marcia R. ; Hellmich, Helen ; Turner, Mary ; Nguyen, Ngoc Bich ; Vadigepalli, Rajanikanth ; Dyer, David W. ; Hurst, Robert E. ; Centola, Michael ; Saban, Ricardo. / The inflammatory and normal transcriptome of mouse bladder detrusor and mucosa. In: BMC Physiology. 2006 ; Vol. 6.
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