title: Post-Natal Inhibition of NF-κB Activation Prevents Renal Damage Caused by Prenatal LPS Exposure.
abstract: Prenatal exposure to an inflammatory stimulus has been shown to cause renal damage in offspring. Our present study explored the role of intra-renal NF-κB activation in the development of progressive renal fibrosis in offspring that underwent prenatal exposure to an inflammatory stimulus. Time-dated pregnant rats were treated with saline (control group) or 0.79 mg/kg lipopolysaccharide (LPS) through intra-peritoneal injection on gestational day 8, 10 and 12. At the age of 7 weeks, offspring from control or LPS group were treated with either tap water (Con+Ve or LPS+Ve group) or pyrollidine dithiocarbamate (PDTC, 120 mg/L), a NF-κB inhibitor, via drinking water starting (Con+PDTC or LPS+PDTC group), respectively, till the age of 20 or 68 weeks. The gross structure of kidney was assessed by hematoxylin-eosin, periodic acid-Schiff staining and Sirius red staining. The expression levels of TNF-α, IL-6, α-smooth muscle actin (α-SMA) and renin-angiotensin system (RAS) genes were determined by real time polymerase chain reaction and/or immunohistochemical staining. Our data showed that post-natal persistent PDTC administration efficiently repressed intra-renal NF-κB activation, TNF-α and IL-6 expression. Post-natal PDTC also prevented intra-renal glycogen deposition and collagenous fiber generation as evident by the reduced expression of collagen III and interstitial α-SMA in offspring of prenatal LPS exposure. Furthermore, post-natal PDTC administration reversed the intra-renal renin-angiotensin system (RAS) over-activity in offspring of prenatal LPS exposure. In conclusion, prenatal inflammatory exposure results in offspring's intra-renal NF-κB activation along with inflammation which cross-talked with excessive RAS activation that caused exacerbation of renal fibrosis and dysfunction in the offspring. Thus, early life prevention of NF-κB activation may be a potential preventive strategy for chronic renal inflammation and progressive renal damage.
authors.affiliation: Institute of Materia Medica, College of Pharmacy, Third Military Medical University, Chongqing 400038, China.|Department of Pharmacy, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Guo
authors.affiliation: Institute of Materia Medica, College of Pharmacy, Third Military Medical University, Chongqing 400038, China.|Center of Translational Medicine, College of Pharmacy, Third Military Medical University, Chongqing 400038, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Guan
authors.affiliation: Institute of Materia Medica, College of Pharmacy, Third Military Medical University, Chongqing 400038, China.|Center of Translational Medicine, College of Pharmacy, Third Military Medical University, Chongqing 400038, China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Pan
authors.affiliation: Institute of Materia Medica, College of Pharmacy, Third Military Medical University, Chongqing 400038, China.|Center of Translational Medicine, College of Pharmacy, Third Military Medical University, Chongqing 400038, China.
authors.forename: Xiongshan
authors.initials: X
authors.lastname: Sun
authors.affiliation: Institute of Materia Medica, College of Pharmacy, Third Military Medical University, Chongqing 400038, China.|Center of Translational Medicine, College of Pharmacy, Third Military Medical University, Chongqing 400038, China.
authors.forename: Fangjie
authors.initials: F
authors.lastname: Wang
authors.affiliation: Institute of Materia Medica, College of Pharmacy, Third Military Medical University, Chongqing 400038, China.|Center of Translational Medicine, College of Pharmacy, Third Military Medical University, Chongqing 400038, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Ji
authors.affiliation: Institute of Materia Medica, College of Pharmacy, Third Military Medical University, Chongqing 400038, China.|Center of Translational Medicine, College of Pharmacy, Third Military Medical University, Chongqing 400038, China.
authors.forename: Pei
authors.initials: P
authors.lastname: Huang
authors.affiliation: Institute of Materia Medica, College of Pharmacy, Third Military Medical University, Chongqing 400038, China.|Center of Translational Medicine, College of Pharmacy, Third Military Medical University, Chongqing 400038, China.
authors.forename: Yafei
authors.initials: Y
authors.lastname: Deng
authors.affiliation: Institute of Materia Medica, College of Pharmacy, Third Military Medical University, Chongqing 400038, China.|Center of Translational Medicine, College of Pharmacy, Third Military Medical University, Chongqing 400038, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Institute of Materia Medica, College of Pharmacy, Third Military Medical University, Chongqing 400038, China.|Center of Translational Medicine, College of Pharmacy, Third Military Medical University, Chongqing 400038, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Han
authors.affiliation: Department of Obstetrics and Gynecology, Daping Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Yi
authors.affiliation: Colleges of Pharmacy and Medicine, University of Manitoba, Apotex Center 750, McDermot Avenue, Winnipeg, R3E 0T5, MB, Canada.|Joint Laboratory of Biological Psychiatry between Shantou University Medical College and the College of Medicine University of Manitoba, Shantou 515063, China.
authors.forename: Michael
authors.initials: M
authors.lastname: Namaka
authors.affiliation: Institute of Materia Medica, College of Pharmacy, Third Military Medical University, Chongqing 400038, China.|Center of Translational Medicine, College of Pharmacy, Third Military Medical University, Chongqing 400038, China.
authors.forename: Ya
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Institute of Materia Medica, College of Pharmacy, Third Military Medical University, Chongqing 400038, China.|Center of Translational Medicine, College of Pharmacy, Third Military Medical University, Chongqing 400038, China.
authors.forename: Youcai
authors.identifier: http://orcid.org/0000-0001-5488-8576
authors.initials: Y
authors.lastname: Deng
authors.affiliation: Institute of Materia Medica, College of Pharmacy, Third Military Medical University, Chongqing 400038, China.|Center of Translational Medicine, College of Pharmacy, Third Military Medical University, Chongqing 400038, China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Li
mesh_terms: D000818:Animals; D005260:Female; D005355:Fibrosis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008070:Lipopolysaccharides; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000378:metabolism* / Q000473:pathology; D011759:Pyrrolidines / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D013859:Thiocarbamates / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D008070:Lipopolysaccharides; D016328:NF-kappa B; D011759:Pyrrolidines; D013859:Thiocarbamates; C020972:pyrrolidine dithiocarbamic acid