Hyperplasia and squamous metaplasia in the tracheobronchial epithelium: alterations in the balance of growth and differentiation factors.

The tracheobronchial epithelium is a continuously self-renewing columnar, pseudo-stratified epithelium. During regular turnover of this epithelium, terminally differentiated cells are replaced through the proliferation and differentiation of progenitor cells (1). Under normal conditions, the rate of renewal is relatively slow. To maintain the normal structure of the epithelium, the rates of proliferation and differentiation and cell loss must be equal. Various growth and differentiation factors, including several polypeptide growth factors, cytokines, and retinoids, cooperate to maintain this balance. During development, a different balance of growth and differentiation factors is required to sustain the rapid growth of the tissue. Changes in the synthesis or activation of these factors are one likely cause of increased proliferation under certain pathologic conditions, including hyperplasia, squamous metaplasia, and neoplasia. The tracheobronchial epithelium contains several cell types (basal, neuroendocrine, and mucous cells) that are able to undergo mitosis. Increased proliferation of these cell types may lead to either basal cell, mucous cell, or neuroendocrine cell hyperplasia. It is likely that the hyperproliferation of these three cell types is regulated differently and controlled by different factors. In this chapter, we will focus on studies designed to understand basal cell hyperplasia.