Microarray analysis of exstrophic human bladder smooth muscle

Jason Hipp, Karl Erik Andersson, Tae Gyun Kwon, Eun Kyoung Kwak, James Yoo, Anthony Atala

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

OBJECTIVE: To compare the genetic profiles of 'healthy' bladder smooth muscle cells (SMCs) and exstrophic SMCs (ESMCs) to identify genes that are over- and under-expressed in ESMCs, thus providing a molecular evaluation of the quality and therapeutic potential of ESMC tissue. PATIENTS, MATERIAL AND METHODS: Classical bladder exstrophy is a rare disorder, occurring in 1 in 30 000 live births. Studies have shown that exstrophic bladders are developmentally immature at birth. After surgical closure, the bladder typically undergoes abnormal remodelling (such as over-expression of collagen III) throughout early development. We hypothesized that the predominant genetic differences between normal SMCs and ESMCs are in the developmental genes. This hypothesis was tested by the use of microarray analysis. Bladder SM biopsies were taken from 'healthy' subjects undergoing bladder surgeries for other conditions (for example, urinary reflux) and patients with bladder exstrophy. Cells were expanded in vitro, and total RNA was isolated and hybridized to the Affymetrix U133A GeneChip® (Affymetrix Inc., Santa Clara, CA, USA) by the Wake Forest University School of Medicine Affymetrix core facility, using standard protocols. RESULTS: We created a genetic signature consisting of 961 genes that are over-expressed and 432 genes that are under-expressed in ESMCs. Analysis of these signatures identified an over-expression of inflammatory genes and an under-expression of developmental genes. CONCLUSION: Our data is in concordance with previous studies and histological data showing that ESMCs are developmentally immature relative to healthy bladder SM. The clinical implication of the ESMC genetic signature is that it provides a list of targets that can be (i) manipulated ex vivo and/or in vivo to induce differentiation (the completion of development) and (ii) used as biomarkers to explain the variability of the clinical symptoms after surgical closure.

Original languageEnglish
Pages (from-to)100-105
Number of pages6
JournalBJU International
Volume101
Issue number1
DOIs
StatePublished - Jan 1 2008
Externally publishedYes

Fingerprint

Microarray Analysis
Smooth Muscle
Urinary Bladder
Bladder Exstrophy
Smooth Muscle Myocytes
Developmental Genes
Genes
Live Birth
Healthy Volunteers
Collagen
Biomarkers
Medicine
Parturition
RNA
Biopsy
Gene Expression

Keywords

  • Affymetrix
  • Bladder exstrophy
  • Microarray
  • Smooth muscle

ASJC Scopus subject areas

  • Urology

Cite this

Hipp, J., Andersson, K. E., Kwon, T. G., Kwak, E. K., Yoo, J., & Atala, A. (2008). Microarray analysis of exstrophic human bladder smooth muscle. BJU International, 101(1), 100-105. https://doi.org/10.1111/j.1464-410X.2007.07211.x

Microarray analysis of exstrophic human bladder smooth muscle. / Hipp, Jason; Andersson, Karl Erik; Kwon, Tae Gyun; Kwak, Eun Kyoung; Yoo, James; Atala, Anthony.

In: BJU International, Vol. 101, No. 1, 01.01.2008, p. 100-105.

Research output: Contribution to journalArticle

Hipp, J, Andersson, KE, Kwon, TG, Kwak, EK, Yoo, J & Atala, A 2008, 'Microarray analysis of exstrophic human bladder smooth muscle', BJU International, vol. 101, no. 1, pp. 100-105. https://doi.org/10.1111/j.1464-410X.2007.07211.x
Hipp J, Andersson KE, Kwon TG, Kwak EK, Yoo J, Atala A. Microarray analysis of exstrophic human bladder smooth muscle. BJU International. 2008 Jan 1;101(1):100-105. https://doi.org/10.1111/j.1464-410X.2007.07211.x
Hipp, Jason ; Andersson, Karl Erik ; Kwon, Tae Gyun ; Kwak, Eun Kyoung ; Yoo, James ; Atala, Anthony. / Microarray analysis of exstrophic human bladder smooth muscle. In: BJU International. 2008 ; Vol. 101, No. 1. pp. 100-105.
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