TY - JOUR T1 - Role of Transforming Growth Factor β in Rat Bladder Smooth Muscle Cell Proliferation JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 117 LP - 122 DO - 10.1124/jpet.106.119115 VL - 322 IS - 1 AU - Maurits M. Barendrecht AU - Arthur C. M. Mulders AU - Henk van der Poel AU - Maurice J. B. van den Hoff AU - Martina Schmidt AU - Martin C. Michel Y1 - 2007/07/01 UR - http://jpet.aspetjournals.org/content/322/1/117.abstract N2 - Conditions associated with hypertrophy of the urinary bladder have repeatedly been associated with an increased urinary excretion of transforming growth factor (TGF) β in both rats and patients. Because TGFβ can have both growth-promoting and -inhibiting effects, we have studied its effects on cell growth and death in primary cultures of rat bladder smooth muscle cells. TGFβ1, TGFβ2, or TGFβ3 did not cause apoptosis, but all three isoforms inhibited DNA synthesis with similar potency (EC50 of approximately 0.1 ng/ml) and efficacy. Such inhibition was antagonized by a specific TGFβ receptor antagonist and independent of the presence of serum. Mitogen-activated protein kinases (MAPKs) are involved in the control of cell growth, and all three TGFβ isoforms inhibited activation of the extracellular signal-regulated kinase, c-Jun NH2-terminal kinase, and p38 MAPK subfamilies. Nevertheless, the inhibitory effects of the TGFβ isoforms on DNA synthesis were not affected by presence of inhibitors of the three MAPK pathways. TGFβ did not alter cell size as measured by flow cytometry or mitochondrial activity, an integrated measure of cell size and number. We conclude that our data do not support the hypothesis that TGFβ is a mediator of rat bladder hypertrophy. The American Society for Pharmacology and Experimental Therapeutics ER -