GSE167567
Effect of in utero nicotine exposure and elastase instillation on transcriptomic profile at post-elastase day 3 in mice
Purpose: The goal of this study is to address if in utero and early life nicotine exposure can affect genetic profile in early ephysema Methods:  A mouse model of two hits: a prenatal hit and a later insult delivered in adulthood was used in this study. In brief, Nicotine (200 mg/L) was supplied immediately after mating and administered to the females in drinking water supplemented with 2% saccharin for the whole period of gestation and until the post-natal day 16 (nicotine group). As a control, we used drinking water with 2% saccharin (control group). Pups born from nicotine-exposed or control mothers were intranasally instilled with elastase or saline at the age of 11 weeks and sacrificed at post-elastase day (ped) 3. Whole lung were collected at ped3 and total RNA was sequenced. We had 4 different groups: control_saline (C-S), control_elastase (C-E), nicotine_saline (N-S) and nicotine_elastase (N-E). ALl the groups had 3 replicas, except N-E group that had 5 different replicas. Results: At ped3 nicotine upregulated 219 and 2 and downregulated 2 and 109 genes in saline and elastase-instilled samples respectively. Elastase upregulated 723 and 439 and downregulated 116 and 77 genes in controls and nicotine-pretreated samples respectively. Pathway analysis performed with MetaCore software (https://portal.genego.com/) (fold change of 2 or more and p<0.05) revealed many identical pathway activated by elastase instillation in both controls and nicotine-pretreated samples such as the cell cycle, DNA damage and cell adhesion, but also revieled the main difference in activation of the immune system between the controls and nicotine-pretreated samples. Conclusions: Our results identify the the early nicotine exposure as an important insult that affects the proteomic signature at ped3 Overall design: Lung mRNA profiles of wild type (WT) C57BL/6J mouse lungs were generated using single-end reads with Illumina HiSeq