The Effect of Epigenetic Therapy on Congenital Neurogenic Bladders-A Pilot Study

Steve J. Hodges, James J. Yoo, Nilamadhab Mishra, Anthony Atala

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Objectives: To demonstrate that human smooth muscle cells derived from neurogenic bladders produce more collagen in vitro than smooth muscle cells derived from normal bladders, and that epigenetic therapy may normalize this increased collagen production. Methods: Human smooth muscle cells from normal (n = 3) and neurogenic bladders (n = 3) were cultured in normal culture media and at different concentrations of the histone deacetylase inhibitors trichostatin A, valproic acid, and the DNA methylation inhibitor 5-azacytidine (5-aza). Collagen type I and III gene expression was measured using real-time quantitative reverse transcription-polymerase chain reaction after varying doses of drug exposure. Cell viability was measured using trypan blue. Results: The smooth muscle cells from neurogenic bladders released significantly more collagen than the normal bladder cells (mean 4.1 vs 1.8 μg/mL in control media) when grown in normal conditions. Treatment with trichostatin A at 50 ng/mL decreased the collagen level in cells from neurogenic bladders to almost normal levels (2.1 μg/mL). In addition, valproic acid treatment decreased collagen types I and III gene expression relative to controls, with maximal effect at 300 mg/mL. These treatments had little effect on cell viability. Conclusions: Histone deacetylase inhibitors decreased collagen production of smooth muscle cells from neurogenic bladders in vitro. These agents may be a means of effectively preventing bladder fibrosis in patients with this condition.

Original languageEnglish (US)
Pages (from-to)868-872
Number of pages5
JournalUrology
Volume75
Issue number4
DOIs
StatePublished - Apr 2010

ASJC Scopus subject areas

  • Urology

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