Article
Biochemistry & Molecular Biology
Edgar Ontsouka, Alessandra Epstein, Sampada Kallol, Jonas Zaugg, Marc Baumann, Henning Schneider, Christiane Albrecht
Summary: The study found significant alterations in placental SLCO3A1 (OATP3A1) gene expression in patients with intrahepatic cholestasis of pregnancy (ICP), while the expression levels of the other 20 genes were comparable between healthy and ICP placentae. Additionally, certain genes in ICP placentae showed positive correlations with BA concentrations and maternal body mass index.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Medicine, Research & Experimental
Qiong Pan, Gang Luo, Jiaquan Qu, Sheng Chen, Xiaoxun Zhang, Nan Zhao, Jingjing Ding, Hong Yang, Mingqiao Li, Ling Li, Ying Cheng, Xuan Li, Qiaoling Xie, Qiao Li, Xueqian Zhou, Huiling Zou, Shijun Fan, Lingyun Zou, Wei Liu, Guohong Deng, Shi-Ying Cai, James L. Boyer, Jin Chai
Summary: The homozygous mutation of SEMA7A(R145W) leads to intrahepatic cholestasis in both mice and children, with further studies showing that this mutation affects the expression of hepatic bile acid transporters and export pumps.
EMBO MOLECULAR MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Elodie Mareux, Martine Lapalus, Amel Ben Saad, Renaud Zelli, Mounia Lakli, Yosra Riahi, Marion Almes, Manon Banet, Isabelle Callebaut, Jean-Luc Decout, Thomas Falguieres, Emmanuel Jacquemin, Emmanuel Gonzales
Summary: The study investigated the mutations of the ABCB11 gene in PFIC2 patients and their functional rescue using specific drugs, providing new pharmacological approaches for treating ABCB11 deficiencies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Gastroenterology & Hepatology
Suilma Ivette Perez-Pineda, Lidia Baylon-Pacheco, Patricia Espiritu-Gordillo, Victor Tsutsumi, Jose Luis Rosales-Encina
Summary: This study investigated the mRNA and protein expression of MRP4 and MRP3 transporters in an in vitro model of cholestasis using the HepG2 cell line. The results showed that primary bile acids CDCA and CA induce overexpression of MRP4 and MRP3 in response to bile acid overload, playing a crucial role in protective and adaptive responses.
ANNALS OF HEPATOLOGY
(2021)
Review
Pharmacology & Pharmacy
Peter Tatrai, Franciska Erdo, Peter Krajcsi
Summary: Bile acids and bile salts (BA/BS) are transported by influx and efflux transporters on hepatocytes, which play crucial roles in bile flow and liver injury. Inhibition of these transporters, especially BSEP, should be tested in early drug development to minimize the risk of drug-induced liver injury (DILI). In vitro test systems for these transporters employ membrane vesicles and whole cells. In addition, cellular toxicity tests using hepatocytes, assessments of mitochondrial toxicity and accumulation of reactive oxygen species (ROS), and inhibition of FXR function are included in pharmaceutical testing panels.
Review
Biochemistry & Molecular Biology
Laszlo Homolya
Summary: Mutations and polymorphisms in the human ABCG2 transporter can lead to reduced function, potentially causing hyperuricemia and toxic reactions. The genetic alterations in ABCG2 can affect the body's defense mechanisms and the absorption, distribution, and excretion of toxic substances.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Toxicology
Hong Feng, Yan Hu, Shaoyu Zhou, Yuanfu Lu
Summary: Knockout of FXR can alleviate OA-induced cholestatic liver injury in mice by reducing bile acid accumulation in the liver and serum, increasing bile acid export via bile, and upregulating bile acid detoxification enzymes.
JOURNAL OF APPLIED TOXICOLOGY
(2022)
Letter
Genetics & Heredity
Elodie Mareux, Martine Lapalus, Amel Ben-Saad, Isabelle Callebaut, Thomas Falguieres, Emmanuel Gonzales, Emmanuel Jacquemin
Summary: The study found that the ABCB11 p.A257V variant exhibits varying functional defects in different cells in vitro, and this defect can be fully rescued by Ivacaftor. This suggests that Ivacaftor may be an effective pharmacological tool for patients with ICP and PFIC2 caused by ABCB11 variations affecting ABCB11 function.
ORPHANET JOURNAL OF RARE DISEASES
(2021)
Article
Plant Sciences
Shasha Qin, Jingzhuo Tian, Yong Zhao, Lianmei Wang, Jinyu Wang, Suyan Liu, Jing Meng, Fang Wang, Chenyue Liu, Jiayin Han, Chen Pan, Yushi Zhang, Yan Yi, Chunying Li, Meiting Liu, Aihua Liang
Summary: This study aims to systematically elucidate the mechanism by which Gardenia extract ameliorates ANIT-induced cholestatic liver injury.
JOURNAL OF ETHNOPHARMACOLOGY
(2024)
Review
Medicine, General & Internal
Maciej Majsterek, Magdalena Wierzchowska-Opoka, Inga Makosz, Lena Kreczynska, Zaneta Kimber-Trojnar, Bozena Leszczynska-Gorzelak
Summary: Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-related condition characterized by elevated levels of bile acids (BAs) in blood serum and an increased risk of adverse perinatal outcomes. Early diagnosis and prompt management based on BA levels are crucial in reducing fetal complications.
Article
Cell Biology
Shang-Hsin Wu, Mei-Hwei Chang, Ya-Hui Chen, Hui-Lin Wu, Huey-Huey Chua, Chin-Sung Chien, Yen-Hsuan Ni, Hui-Ling Chen, Huey-Ling Chen
Summary: This study identified charged multivesicular body protein 5 (CHMP5) as a molecule that interacts with BSEP, affecting its canalicular targeting and retention, resulting in impaired post-Golgi trafficking and bile acid secretion. These findings suggest that ESCRT-III-mediated BSEP sorting is essential for the trafficking of apical membrane proteins, providing new targets for therapeutic interventions in BSEP-associated cholestasis.
JOURNAL OF BIOMEDICAL SCIENCE
(2021)
Article
Biotechnology & Applied Microbiology
Guichun Liu, Wei Liu, Ruoping Zhao, Jinwu He, Zhiwei Dong, Lei Chen, Wenting Wan, Zhou Chang, Wen Wang, Xueyan Li
Summary: The study identified multiple ABC transporter and Rab protein family members in the genome of the swallowtail butterfly, revealing their significant role in body coloration. This provides new insights into the morphological development of butterflies.
Review
Obstetrics & Gynecology
Antonio F. Saad, Luis D. Pacheco, Lucy Chappell, George R. Saade
Summary: ICP is associated with poor perinatal outcomes in some women, but recent evidence shows that UDCA may not have a significant impact on most perinatal outcomes, therefore a comprehensive approach is needed to manage ICP effectively.
REPRODUCTIVE SCIENCES
(2022)
Article
Gastroenterology & Hepatology
Sandra M. W. van de Wiel, Begona Porteiro, Saskia C. Belt, Esther W. M. Vogels, Isabelle Bolt, Jacqueline L. M. Vermeulen, D. Rudi de Waart, Joanne Verheij, Vanesa Muncan, Ronald P. J. Oude Elferink, Stan F. J. van de Graaf
Summary: This study highlights the pivotal role of OSTb in bile acid transport in the ileum. Knockout of Ostb showed a worsened phenotype in cholestasis compared to Ost alpha(-/-) mice, suggesting a distinct role of OSTb in influencing survival and liver phenotype.
Review
Biochemistry & Molecular Biology
Giovanni Vitale, Alessandro Mattiaccio, Amalia Conti, Sonia Berardi, Vittoria Vero, Laura Turco, Marco Seri, Maria Cristina Morelli
Summary: Idiosyncratic Drug-Induced Liver Injury (iDILI) is a significant health challenge, accounting for a high percentage of hepatitis and acute fulminant hepatic failure cases. It has been found that approximately 30% of iDILI cases are cholestatic, with drugs inhibiting specific transport proteins responsible for bile salt export and bile acids' metabolism and transport. Understanding the molecular pathways and links with familial intrahepatic cholestasis is crucial in identifying the main cholestasis-inducing drugs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)