Roles of PPARγ/NF-κB signaling pathway in the pathogenesis of intrahepatic cholestasis of pregnancy.
BACKGROUND
Intrahepatic cholestasis of pregnancy (ICP) is the most prevalent pregnancy specific liver disease. However, the pathogenesis and etiology of ICP is poorly understood.


OBJECTIVE
To assess the expression of peroxisome proliferator-activated receptorγ (PPARγ) and nuclear factor kappa B (NF-κB) in placenta and HTR-8/SVneo cell, and evaluate the serum levels of cytokines, bile acids, hepatic function and lipids in control and ICP patients and the fetal outcome, in order to explore the role of PPARγ/NF-κB signaling pathway in the possible mechanism of ICP.


METHODS
Clinical data of the pregnant women were collected and serum levels of cytokines, bile acids, hepatic function and lipids were measured. Expressions of PPARγ and NF-κB in placenta and HTR-8/SVneo cell were determined. The new-born information was collected to demonstrate the relationship between PPARγ/NF-κB signaling pathway and ICP.


RESULTS
The serum levels of bile acids, hepatic function, triglycerides (TG), total cholesterol (TC), IL-6, IL-12 and TNF-α in ICP group were significantly increased (P<0.01), and serum level of IL-4 was significantly decreased (P<0.01). PPARγ and NF-κB staining were found in the membrane and cytoplasm of placental trophoblast cell. The expression of PPARγ and NF-κB were significantly higher in ICP group and taurocholate acid (TCA) treated HTR-8/SVneo cell (P<0.01). The new-born information in severe ICP group were significantly different as compared to that in control group (P<0.05), and part of information in mild ICP group were also difference to that in control group (P<0.05).


CONCLUSIONS
The higher expressions of PPARγ and NF-κB in ICP placenta and TCA treated HTR-8/SVneo cell, together with the abnormal serum levels of cytokines, might induced by the imbalance of inflammatory and immune reaction, and then disturb placental bile acid and serum lipids transportation, finally result in fatal cholestasis which probably be one of the mechanism of ICP.
Department of Gynecology and Obstetrics, Wuxi Maternal and Child Health Hospital, the Affiliated Hospital of Nanjing Medical University, Wuxi, Jiangsu, China ; Department of Pharmacology, College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu, China.
Yan
Y
Zhang
Department of Gynecology and Obstetrics, Wuxi Maternal and Child Health Hospital, the Affiliated Hospital of Nanjing Medical University, Wuxi, Jiangsu, China.
Lingqing
L
Hu
Department of Pharmacology, College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu, China.
Yan
Y
Cui
Department of Pharmaceutical, Wuxi People's Hospital, Wuxi, Jiangsu, China.
Zhigang
Z
Qi
Department of Gynecology and Obstetrics, Wuxi Maternal and Child Health Hospital, the Affiliated Hospital of Nanjing Medical University, Wuxi, Jiangsu, China.
Xiaoping
X
Huang
Department of Gynecology and Obstetrics, Wuxi Maternal and Child Health Hospital, the Affiliated Hospital of Nanjing Medical University, Wuxi, Jiangsu, China.
Liyi
L
Cai
Department of Gynecology and Obstetrics, Wuxi Maternal and Child Health Hospital, the Affiliated Hospital of Nanjing Medical University, Wuxi, Jiangsu, China.
Ting
T
Zhang
Department of Gynecology and Obstetrics, Wuxi Maternal and Child Health Hospital, the Affiliated Hospital of Nanjing Medical University, Wuxi, Jiangsu, China.
Yongxiang
Y
Yin
Department of Obstetrics and Gynecology, Wuxi Hospital of Traditional Chinese Medicine, Wuxi, Jiangsu, China.
Zhiyi
Z
Lu
Department of Gynecology and Obstetrics, Wuxi Maternal and Child Health Hospital, the Affiliated Hospital of Nanjing Medical University, Wuxi, Jiangsu, China.
Jingying
J
Xiang
D000328:Adult; D016022:Case-Control Studies; D002460:Cell Line; D002780:Cholestasis, Intrahepatic / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D006801:Humans; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism*; D010920:Placenta / Q000378:metabolism / Q000473:pathology; D011247:Pregnancy; D011248:Pregnancy Complications / Q000378:metabolism*; D015398:Signal Transduction; D014327:Trophoblasts / Q000378:metabolism; D055815:Young Adult
D016328:NF-kappa B; D047495:PPAR gamma