ONTOGENY AND REGULATION OF AQUAPORIN EXPRESSION IN THE OVINE FETAL LUNG

H.Liu², A.Armugan³, K.Jeyaseelan³, S.Hooper⁴, I.Koukoulas¹, E.M.Wintour¹, 1 Howard Florey Institute of Experimental Physiology and Medicine, University of Melbourne, Victoria, 3010; 2 Sun Yat Sen University of Medical Sciences, PR, China; 3 Department of Biochemistry, National University of Singapore, Singapore; 4 Department of Physiology, Monash University ,Clayton, Victoria, Australia.

The fetal lung relies on fluid secretion to maintain growth, and this fluid must be reabsorbed at birth to allow for air-breathing. Aquaporins 1,3,4, and 5 are membranous water channel proteins, found in the post-natal rodent and human lung, but not detected before birth (except for AQP1) in the rat and mouse, and therefore assumed to be unimportant for lung liquid production. The rodent lung is very immature at birth, in contrast to the lung of the ovine fetus, the development of which more closely resembles that of the human fetus. We now report the cloning of the ovine AQPs 4and 5, the detection of both mRNA and protein at high levels well before birth (by day 100; term is ~150d). In lungs taken from chronically-cannulated ovine fetuses, in which lung liquid production was increased by cortisol infusion, for 11 days (120-131), the mRNAs of both AQP1 and AQP5, measured by sensitive and reproducible real time PCR, were significantly (P<0.05) increased; tracheal ligation, from days 118-128, caused a decrease in lung liquid production, and significantly (P<0.05) decreased AQP5 expression. Immunohistochemistry was used to show that protein changes occurred in fetal lung sections, consistent with the mRNA changes. These findings suggest that AQPs could be involved in the production and resorption of lung liquid in long-gestation species, and that interpretation of their potential relevance obtained from mouse studies may not be applicable to all species.