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

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...

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Autores principales:	Tarak Srivastava, Trupti Joshi, Daniel P. Heruth, Mohammad H. Rezaiekhaligh, Robert E. Garola, Jianping Zhou, Varun C. Boinpelly, Mohammed Farhan Ali, Uri S. Alon, Madhulika Sharma, Gregory B. Vanden Heuvel, Pramod Mahajan, Lakshmi Priya, Yuexu Jiang, Ellen T. McCarthy, Virginia J. Savin, Ram Sharma, Mukut Sharma
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/eba3b1af72d249d7980f6ba1dad3729b
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spelling	oai:doaj.org-article:eba3b1af72d249d7980f6ba1dad3729b2021-12-02T18:02:53ZA mouse model of prenatal exposure to Interleukin-6 to study the developmental origin of health and disease10.1038/s41598-021-92751-62045-2322https://doaj.org/article/eba3b1af72d249d7980f6ba1dad3729b2021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-92751-6https://doaj.org/toc/2045-2322Abstract 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.Tarak SrivastavaTrupti JoshiDaniel P. HeruthMohammad H. RezaiekhalighRobert E. GarolaJianping ZhouVarun C. BoinpellyMohammed Farhan AliUri S. AlonMadhulika SharmaGregory B. Vanden HeuvelPramod MahajanLakshmi PriyaYuexu JiangEllen T. McCarthyVirginia J. SavinRam SharmaMukut SharmaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-19 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Tarak Srivastava Trupti Joshi Daniel P. Heruth Mohammad H. Rezaiekhaligh Robert E. Garola Jianping Zhou Varun C. Boinpelly Mohammed Farhan Ali Uri S. Alon Madhulika Sharma Gregory B. Vanden Heuvel Pramod Mahajan Lakshmi Priya Yuexu Jiang Ellen T. McCarthy Virginia J. Savin Ram Sharma Mukut Sharma A mouse model of prenatal exposure to Interleukin-6 to study the developmental origin of health and disease
description	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.
format	article
author	Tarak Srivastava Trupti Joshi Daniel P. Heruth Mohammad H. Rezaiekhaligh Robert E. Garola Jianping Zhou Varun C. Boinpelly Mohammed Farhan Ali Uri S. Alon Madhulika Sharma Gregory B. Vanden Heuvel Pramod Mahajan Lakshmi Priya Yuexu Jiang Ellen T. McCarthy Virginia J. Savin Ram Sharma Mukut Sharma
author_facet	Tarak Srivastava Trupti Joshi Daniel P. Heruth Mohammad H. Rezaiekhaligh Robert E. Garola Jianping Zhou Varun C. Boinpelly Mohammed Farhan Ali Uri S. Alon Madhulika Sharma Gregory B. Vanden Heuvel Pramod Mahajan Lakshmi Priya Yuexu Jiang Ellen T. McCarthy Virginia J. Savin Ram Sharma Mukut Sharma
author_sort	Tarak Srivastava
title	A mouse model of prenatal exposure to Interleukin-6 to study the developmental origin of health and disease
title_short	A mouse model of prenatal exposure to Interleukin-6 to study the developmental origin of health and disease
title_full	A mouse model of prenatal exposure to Interleukin-6 to study the developmental origin of health and disease
title_fullStr	A mouse model of prenatal exposure to Interleukin-6 to study the developmental origin of health and disease
title_full_unstemmed	A mouse model of prenatal exposure to Interleukin-6 to study the developmental origin of health and disease
title_sort	mouse model of prenatal exposure to interleukin-6 to study the developmental origin of health and disease
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/eba3b1af72d249d7980f6ba1dad3729b
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A mouse model of prenatal exposure to Interleukin-6 to study the developmental origin of health and disease

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