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- Title
A mouse model of prenatal exposure to Interleukin-6 to study the developmental origin of health and disease.
- Authors
Srivastava, Tarak; Joshi, Trupti; Heruth, Daniel P.; Rezaiekhaligh, Mohammad H.; Garola, Robert E.; Zhou, Jianping; Boinpelly, Varun C.; Ali, Mohammed Farhan; Alon, Uri S.; Sharma, Madhulika; Vanden Heuvel, Gregory B.; Mahajan, Pramod; Priya, Lakshmi; Jiang, Yuexu; McCarthy, Ellen T.; Savin, Virginia J.; Sharma, Ram; Sharma, Mukut
- 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.
- Subjects
INTERLEUKIN-6; INFLAMMATION; MATERNAL health; CHRONIC kidney failure; LABORATORY mice; PRENATAL exposure
- Publication
Scientific Reports, 2021, Vol 11, Issue 1, p1
- ISSN
2045-2322
- Publication type
Article
- DOI
10.1038/s41598-021-92751-6