Post-Natal Inhibition of NF-κB Activation Prevents Renal Damage Caused by Prenatal LPS Exposure

• Published in: PloS one 2016-04, Vol.11 (4), p.e0153434-e0153434
• Main Authors: Guo, Wei, Guan, Xiao, Pan, Xiaodong, Sun, Xiongshan, Wang, Fangjie, Ji, Yan, Huang, Pei, Deng, Yafei, Zhang, Qi, Han, Qi, Yi, Ping, Namaka, Michael, Liu, Ya, Deng, Youcai, Li, Xiaohui
• Format: Article
• Language: English
• Subjects: Actin; Activation; Angiotensin; Animals; Biology and Life Sciences; Cardiovascular disease; Collagen (type III); Cytokines; Damage prevention; Drinking water; Exposure; Female; Fibrosis; Fibrosis - chemically induced; Fibrosis - metabolism; Fibrosis - pathology; Fibrosis - prevention & control; Gene expression; Genetic crosses; Glycogen; Hypertension; Immunology; Independent drug stores; Inflammation; Interleukin 6; Kidney - drug effects; Kidney - metabolism; Kidney - pathology; Kidney diseases; Kidneys; Lipopolysaccharides; Medicine; Medicine and Health Sciences; Muscles; NF-kappa B - antagonists & inhibitors; NF-κB protein; Offspring; Peritoneum; Pharmacy; Polymerase chain reaction; Pregnancy; Prenatal experience; Prenatal exposure; Prenatal Exposure Delayed Effects - metabolism; Prenatal Exposure Delayed Effects - pathology; Pyrrolidines - pharmacology; Pyrrolidines - therapeutic use; Rats; Rats, Sprague-Dawley; Renal function; Renin; Research and Analysis Methods; Rodents; Signal Transduction - drug effects; Smooth muscle; Staining; Thiocarbamates - pharmacology; Thiocarbamates - therapeutic use; Tumor necrosis factor-α; Water treatment
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0153434

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.