Collagen Directly Stimulates Bladder Smooth Muscle Cell Growth In Vitro: Regulation by Extracellular Regulated Mitogen Activated Protein Kinase

ABSTRACTPurpose: Bladders clinically subjected to excessive pressure or distention demonstrate an altered extracellular matrix (ECM) composition. We determined how an altered collagen substratum might affect bladder smooth muscle cell (bSMC) growth in vitro and probed the mechanism of this response.Materials and Methods: Primary culture rat bSMCs were seeded onto culture plates pre-coated with normal type I collagen (NC) or heat denatured type I collagen (DNC) under standard culture conditions. In separate experiments bSMCs from the 2 substrates were enzymatically released and changed to growth on normal collagen (NC→NC or DNC→NC) or denatured collagen (DNC→DNC or NC→DNC). At 24 hours proliferation was assessed by 3H-thymidine incorporation. Statistical significance in triplicate wells was determined by ANOVA.Results: The proliferation of bSMCs on DNC was 5-fold greater than on NC (p <0.0001). Passage onto damaged collagen (DNC→DNC) showed 2-fold further augmentation in proliferation (p <0.0001) but only ...