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.In children with myelodysplasia, a primary concern is the maintenance of low bladder storage pressure. Elevated intravesical pressure caused by a poorly compliant bladder in patients with spinal dysraphism is associated with damage to the upper urinary tract, and if not appropriately treated, renal failure. 1 Many treatment modalities have been developed to prevent or treat this disease process. One example is the use of chronic oral antimuscarinic therapy from an early age, coupled with clean intermittent catheterization. 2 Intravesical instillation of oxybutynin and other agents also has been attempted. 3,4 However, these therapies vary in efficacy and are associated with a number of side effects. Thus, development of novel treatment options is desirable.Neuropathic bladders have an increased ratio of type-III to type-I collagen, with an absolute increase in the amount of type-III collagen. 5 This increased collagen content is at least in part produced by detrusor smooth muscle cells and is thought to be a major cause of