[HTML][HTML] A mouse model of prenatal exposure to Interleukin-6 to study the developmental origin of health and disease

T Srivastava, T Joshi, DP Heruth, MH Rezaiekhaligh… - Scientific Reports, 2021 - nature.com
T Srivastava, T Joshi, DP Heruth, MH Rezaiekhaligh, RE Garola, J Zhou, VC Boinpelly
Scientific Reports, 2021nature.com
Systemic inflammation in pregnant obese women is associated with 1.5-to 2-fold increase in
serum Interleukin-6 (IL-6) and newborns with lower kidney/body weight ratio but the role of
IL-6 in increased susceptibility to chronic kidney (CKD) in adult progeny is not known. Since
IL-6 crosses the placental barrier, we administered recombinant IL-6 (10 pg/g) to pregnant
mice starting at mid-gestation yielded newborns with lower body (p< 0.001) and kidney (p<
0.001) weights. Histomorphometry indicated decreased nephrogenic zone width (p= 0.039) …
Abstract
Systemic inflammation in pregnant obese women is associated with 1.5- to 2-fold increase in serum Interleukin-6 (IL-6) and newborns with lower kidney/body weight ratio but the role of IL-6 in increased susceptibility to chronic kidney (CKD) in adult progeny is not known. Since IL-6 crosses the placental barrier, we administered recombinant IL-6 (10 pg/g) to pregnant mice starting at mid-gestation yielded newborns with lower body (p < 0.001) and kidney (p < 0.001) weights. Histomorphometry indicated decreased nephrogenic zone width (p = 0.039) with increased numbers of mature glomeruli (p = 0.002) and pre-tubular aggregates (p = 0.041). Accelerated maturation in IL-6 newborns was suggested by early expression of podocyte-specific protein podocin in glomeruli, increased 5-methyl-cytosine (LC–MS analysis for CpG DNA methylation) and altered expression of certain genes of cell-cycle and apoptosis (RT-qPCR array-analysis). Western blotting showed upregulated pJAK2/pSTAT3. Thus, treating dams with IL-6 as a surrogate provides newborns to study effects of maternal systemic inflammation on future susceptibility to CKD in adulthood.
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