However, in most complex organisms, the growth and differentiation of dividing cells are controlled in part by peptide growth factors. These endogenous, biologically active substances are constructed locally and released in a paracrine fashion at their site of action. Previous investigations have supported the involvement of growth factors in the proliferation and differentiation of the ME mucosa during OM. For example, fibroblast growth factors 1 and 2 appear to play a role in the growth, Olprinone hydrochloride hyperproliferation, and differentiation of the stromal compartment of the ME mucosa during OM, but not the mucosal epithelium. While some studies of epidermal growth factor, betacellulin, and keratinocyte growth factor have implicated them in mucosal epithelial proliferation, these represent only a fraction of the growth factors that can influence epithelial cells that might be expressed in the mucosa during OM. We hypothesized that a comprehensive Phenelzine sulfate salt survey of growth factor expression during ME infection, and kinetic analysis to link expression to mucosal hyperplasia, would allow the identification of candidates that underly the growth of the mucosal epithelium, which could then be tested for growth promotion. The hypothesis was tested in widely used mouse and rat models of OM. These species are recognized as sharing the major characteristics of this disease with humans. The goal of the present study was to identify growth factors that are modulated during bacterial OM and which demonstrate the abililty to regulate mucosal epithelial growth. To do so, we used a whole-genome gene array technique across an entire episode of acute OM, focusing on growth factor genes that were expressed just prior to mucosal hyperplasia. We identified seven factors with appropriate expression kinetics. These factors were then tested for their ability to enhance the growth of the ME mucosal epithelium in vitro. Also, we confirmed in vivo expression and distribution of HB-EGF, which induced proliferation in the mucosal epithelium in vitro. In this study, we evaluated growth factors for their potential to induce mucosal epithelial hyperplasia during the course of bacterial OM.