Altered gene expression in rat lung with sequential intramniotic LPS and hyperoxia exposure

This submission has open access
Submission ID :
ESPR367
Submission Type
Submission Topic
Abstract: :

Background: Chorioamnionitis and oxygen exposure in the perinatal period are believed to adversely affect

cell function in lung tissue. We have previously shown altered gene expression in rat pup lungs following either

intramniotic lipopolysaccharide (LPS) injection or postnatal hyperoxia exposure. Sequential exposure to both

LPS followed by hyperoxia may act as a double hit to lung, adversely affecting cellular function and protein

synthesis; which in turn may play a role in pathogenesis of diseases like Bronchopulmonary dysplasia and

asthma.

Objective: To study the alteration of gene expression in lung tissue in a rat model of chorioamnionitis with

subsequent hyperoxia exposure, by analysis of mRNA transcription, compared to no treatment control.

Design/Methods: In the LPS – O2 group, chorioamnionitis was induced by intra-amniotic injection of 1 μg of

LPS in timed pregnant Sprague Dawley rats on gestational day 20 (E20), followed by delivery of the pups on

E22. After 7 days of hyperoxia exposure ( 85% Oxygen), these pups were sacrificed. Control rats (NS-RA

group) were injected with normal saline and kept in room air. Lung tissue was harvested and RNA was isolated

using the Qiagen miRNeasy mini kit. Affymetrix WT-plus Rat Clariom S Gene chip was used to perform

genome wide microarray screening and Transcriptome Array Console and GeneSpring softwares was used to

analyse the data.

Results: We found an alteration of expression in 1958 gene in the LPS-O2 group compared to the NS-RA

group, with up regulation of 904 genes and down regulation of 1054 genes (fold change > 1.5, p-value < 0.05).

Ingenuity Pathway Analysis (IPA) software identified 548 canonical pathways; important pathways were

"Communication between Innate and Adaptive Immune Cells, Th1 and Th2 Activation, Neuroinflammation

Signaling, IL-6 signaling, IL-15 production and Toll Like receptor signalling." Important diseases and functions

affected were "Organismal Development, Cellular Movement, Inflammatory Response, Cell Death and Survival

and Molecular Transport." Two important networks relevant to our study were: "Cell-To-Cell Signaling and

Interaction, Cellular Movement and Immune Cell Trafficking;" and,"Cellular Movement, Hematological System

Development and Function, Immune Cell Trafficking."

Conclusion(s): Sequential exposure to LPS followed by hyperoxia causes differential gene expression in rat

lung tissue, which may alter cellular function contribute to pathogenesis of long term disease processes

Sidney Kimmel Medical College at Thomas Jefferson University
Pediatrics/Neonatology, Thomas Jefferson University/Nemours, Philadelphia, PA, United States
Christiana Care
Pediatrics/Neonatology, Thomas Jefferson University/Nemours, Philadelphia, PA, United States
Christiana Care
Inova Children's Hospital
Pediatrics/Neonatology, Thomas Jefferson University/Nemours, Philadelphia, PA, United States
Thomas Jefferson University
Pediatrics/Neonatology, Thomas Jefferson University/Nemours, Philadelphia, PA, United States
Pediatrics/Neonatology, Thomas Jefferson University/Nemours, Philadelphia, PA, United States
Thomas Jefferson University
Thomas Jefferson University, Philadelphia, PA, United States
Thomas Jefferson Sidney Kimmel Medical College

Similar Abstracts by Type

Submission ID
Submission Title
Submission Topic
Submission Type
Corresponding Author
ESPR157
Clinical Research
Original science
Aditya Chhikara
ESPR302
Epidemiology
Original science
Natasha Jouk
ESPR74
Clinical Research
Original science
Alexandra Mazo