Keratinocyte growth factor as an epithelial protective agent: Where do we stand?

Abstract

7 he discovery of keratinocyte growth factor (KGF) in 1989 1) has contributed greatly to our understanding of the egulation of epithelial proliferation and repair in many rgans, including the lung. KGF, a member of the heparininding fibroblast growth factor family, is a paracrine-actng, epithelial-specific growth factor that is produced preominantly by mesenchymal cells. In the developing lung, GF plays an important role in both branching morphogensis and epithelial differentiation. In the adult lung, KGF is n important mediator of alveolar epithelial proliferation nd repair (2) that is produced predominantly by fibroblasts. ts primary targets are the alveolar and airway epithelium. dministration of exogenous KGF to the normal lung prouces alveolar epithelial type II cell hyperplasia (3), a rocess that resembles the normal repair process after acute lveolar epithelial injury. Shortly after the description of KGF, the first study of xogenous KGF in an acute lung injury model was reported 4). KGF has now been very well studied in a multitude of xperimental models of acute lung injury (2). Intratracheal GF protects against experimental lung injury resulting rom both direct and indirect causes, including hyperoxia, cid aspiration, mechanical ventilation, radiation, bacterial neumonia, graft-vs.-host disease, -naphthylthiourea, and leomycin. The mechanisms of this protective effect have ot been fully elucidated but likely include hyperplasia of lveolar epithelial type II cells, increased surfactant protein roduction, increased alveolar epithelial fluid transport, enanced alveolar epithelial migration and wound repair, and nhanced resistance of the alveolar epithelium to injury. lthough these studies have shown remarkable and reproucible protective effects of KGF, the potential for translaion to clinical therapy has been greatly limited by the need o administer KGF before the injurious insult in all of these xperimental models. In this issue of the Journal, Chen et al. (5) reported the uccessful prevention of late radiation-induced pulmonary