Adam Blair, University of Utah
Physical Sciences
Objectives: Histone covalent modifications influence regulation of gene expression. Changes in histone covalent modifications are triggered by abrupt changes in environment, such as preterm birth followed by mechanical ventilation (MV). Whether histone modifications also occur in the kidney of chronically ventilated preterm lambs is not known. We hypothesized that ventilation of preterm lambs affects histone modification in kidneys.
Methods: Preterm lambs were delivered at ~130d gestation (~29wk human gestation), intubated, and given surfactant and caffeine citrate. They were ventilated by MV or weaned to non-invasive high-frequency nasal ventilation (HFNV) for 3d. Other preterm lambs were weaned from 3d of MV and lived for ~6mo more. Gestational age-matched (fetal and longterm weaning) lambs served as reference groups (n=5/group). Renal cortex was analyzed by immunoblot for H3K9ac, H3K14ac, H3K18ac, H3K4me3, and H3K36me2. Statistical differences were tested by ANOVA and Fisher’s PLSD.
Results: The histone marks had different abundance in the kidney, depending on the lamb group (Fig 1). H3K9ac abundance was significantly lowest for the MV and HFNV groups of preterm lambs, and weaned lambs. Conversely, H3K14ac abundance was significantly highest for the MV and HFNV groups of preterm lambs, and weaned lambs. H3K18ac abundance was significantly highest for the MV group of preterm lambs and weaned lambs. H3K9ac abundance was significantly lowest in the MV and HFNV groups of preterm lambs, and weaned lambs. H3K4me2 was not different among groups. H3k36me3 was significantly lowest for the MV group of preterm lambs.
Conclusions: Histone covalent modifications appear to be altered in the kidney of preterm lambs after MV and HFNV, and some changes persist up to 6 mo of recovery from preterm birth and prolonged ventilation. The fidelity of abundance presumably influences renal function and structure later in life.