Role of alveolar epithelial cell proliferation and surfactant protein in acute lung injury : effect of KGF and artificial surfactant on lung injury

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1.Effect of growth factor for alveolar type II cells on lung injury : We have demonstrated that keratinocyte growth factor (KGF) is a potent factr for proliferation and differentiation of alveolar type II cells (Am J Physiol 269,1995). We have examined whether KGF would prevent bleomycin-induced lung injury and fibrosis. Recombinant human KGF (rhKGF) was injected intratracheally at 48h before and 24h after bleomycin. KGF treatment prevents 1)loss of body weight, 2)reduced total lung capacity, 3)accumulation of collagen type I & III and thier mRNAs, and 4)decreased autoradiographic silver grains for surfactant protein A (SP-A), SP-B and SP-C mRNAs in the rat lungs induced by bleomycin. Lung injury due to acid instillation was also prevented by KGF pretreatment at 72h before acid (0.1N HC1) instillation, but not by posttreatme2) nt. 2.Combined posttreatmental effects of KGF and artificial surfactant on lung injury : The combined instillations of KGF and artificial surfactant 48h after bleomycin or acid didn't change lung injury so much because of the strong pulmonary edema. Therefore, we were examining the better time point of instillation for preventing lung injury, with artificial surfactant. 3.To clarify the mechanisms of prevention, we were examining the expression of the transcription factor, C/EBP family members, and the lungs of C/EBP deficient mice. 4.Prevention of lung injury due to intratracheal instillation of cultured alveolar cells : We are under experiments on whether cultured alveolar epithelial cells stimulated by KGF wouldprevent lung injury and fibrosis. 5.Future project : We are going to study gene transfer of KGF using adeno-virus intratracheally for preventing lung injury and fibrosis.