scholarly journals β-Catenin-NFκB-CFTR interactions in cholangiocytes regulate inflammation and fibrosis during ductular reaction

2021 ◽  
Author(s):  
Shikai Hu ◽  
Jacquelyn Russell ◽  
Silvia Liu ◽  
Ravi Rai ◽  
Karis Kosar ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Epithelial Cells ◽  
Liver Diseases ◽  
Underlying Mechanism ◽  
Complete Understanding ◽  
Ductular Reaction ◽  
Biliary Epithelial Cells ◽  
Liver Repopulation ◽  
Initial Injury

Expansion of biliary epithelial cells (BECs) during ductular reaction (DR) is observed in liver diseases including cystic fibrosis (CF), and associated with inflammation and fibrosis, albeit without complete understanding of underlying mechanism. Using two different genetic knockouts of β-catenin, one with ß-catenin loss is hepatocytes and BECs (KO1), and another with loss in only hepatocytes (KO2), we demonstrate disparate long-term repair after an initial injury by 2-week choline-deficient ethionine supplemented diet. KO2 show gradual liver repopulation with BEC-derived β-cateninpositive hepatocytes, and resolution of injury. KO1 showed persistent loss of β-catenin, NF-κB activation in BECs, progressive DR and fibrosis, reminiscent of Cystic fibrosis (CF) histology. We identify interactions of β-catenin, NFκB and Cystic fibrosis transmembranous conductance regulator (CFTR) in BECs. Loss of CFTR or β-catenin led to NF-κB activation, DR and inflammation. Thus, we report novel β-catenin-NFκBCFTR interactome in BECs, and its disruption may contribute to hepatic pathology of CF.

scholarly journals β-Catenin-NFkB-CFTR interactions in cholangiocytes regulate inflammation and fibrosis during ductular reaction

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Shikai Hu ◽  
Jacquelyn O Russell ◽  
Silvia Liu ◽  
Catherine Cao ◽  
Jackson McGaughey ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Epithelial Cells ◽  
Liver Diseases ◽  
Underlying Mechanism ◽  
Complete Understanding ◽  
Ductular Reaction ◽  
Biliary Epithelial Cells ◽  
Liver Repopulation ◽  
Initial Injury

Expansion of biliary epithelial cells (BECs) during ductular reaction (DR) is observed in liver diseases including cystic fibrosis (CF), and associated with inflammation and fibrosis, albeit without complete understanding of underlying mechanism. Using two different genetic mouse knockouts of b-catenin, one with b-catenin loss is hepatocytes and BECs (KO1), and another with loss in only hepatocytes (KO2), we demonstrate disparate long-term repair after an initial injury by 2-week choline-deficient ethionine-supplemented diet. KO2 show gradual liver repopulation with BEC-derived b-catenin-positive hepatocytes, and resolution of injury. KO1 showed persistent loss of b-catenin, NF-kB activation in BECs, progressive DR and fibrosis, reminiscent of CF histology. We identify interactions of b-catenin, NFkB and CF transmembranous conductance regulator (CFTR) in BECs. Loss of CFTR or b-catenin led to NF-kB activation, DR and inflammation. Thus, we report a novel b-catenin-NFkB-CFTR interactome in BECs, and its disruption may contribute to hepatic pathology of CF.

scholarly journals YAP, but Not RSPO-LGR4/5, Signaling in Biliary Epithelial Cells Promotes a Ductular Reaction in Response to Liver Injury

2019 ◽  
Vol 25 (1) ◽  
pp. 39-53.e10 ◽  
Author(s):  
Lara Planas-Paz ◽  
Tianliang Sun ◽  
Monika Pikiolek ◽  
Nadire R. Cochran ◽  
Sebastian Bergling ◽  
...  
Keyword(s):  
Liver Injury ◽  
Epithelial Cells ◽  
Ductular Reaction ◽  
Biliary Epithelial Cells

Long-Term Cultures of Polarized Airway Epithelial Cells from Patients with Cystic Fibrosis

2006 ◽  
Vol 34 (1) ◽  
pp. 39-48 ◽  
Author(s):  
Ludovic Wiszniewski ◽  
Lan Jornot ◽  
Tecla Dudez ◽  
Alessandra Pagano ◽  
Thierry Rochat ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Epithelial Cells ◽  
Airway Epithelial Cells ◽  
Airway Epithelial

scholarly journals Stromal Cell–Derived Factor-1 from Biliary Epithelial Cells Recruits CXCR4-Positive Cells: Implications for Inflammatory Liver Diseases

2003 ◽  
Vol 83 (5) ◽  
pp. 665-672 ◽  
Author(s):  
Ryo Terada ◽  
Kazuhide Yamamoto ◽  
Tomomi Hakoda ◽  
Noriaki Shimada ◽  
Nobuaki Okano ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Liver Diseases ◽  
Stromal Cell ◽  
Biliary Epithelial Cells ◽  
Stromal Cell Derived Factor

Macrolide Treatment Decreased the Size of Nasal Polyps and IL-8 Levels in Nasal Lavage

2000 ◽  
Vol 14 (3) ◽  
pp. 143-148 ◽  
Author(s):  
Takechiyo Yamada ◽  
Shigeharu Fujieda ◽  
Shigehito Mori ◽  
Hideyuki Yamamoto ◽  
Hitoshi Saito
Keyword(s):  
Cystic Fibrosis ◽  
Epithelial Cells ◽  
Chronic Rhinosinusitis ◽  
Nasal Polyps ◽  
Experimental Studies ◽  
Nasal Lavage ◽  
Nasal Epithelial Cells ◽  
Diffuse Panbronchiolitis ◽  
Human Nasal Epithelial Cells

Recently, epidemiologic and experimental studies have been reported that long-term macrolides are effective for the treatment of chronic airway inflammatory diseases including diffuse panbronchiolitis, chronic rhinosinusitis, and cystic fibrosis (Jaffe A, Francis J, Rosenthal M, et al. Long-term azithromycin may improve lung function in children with cystic fibrosis. Lancet 351:420, 1998), and that macrolides can directly reduce the production of IL-8 by nasal epithelial cells (Suzuki H, Shimomura A, Ikeda K, et al. Inhibitory effect of macrolides on interleukin-8 secretion from cultured human nasal epithelial cells. Laryngoscope 107:1661–1666, 1997). In this study we administered macrolides with 14-membered rings to patients with nasal polyps due to chronic rhinosinusitis for at least 3 months and measured the IL-8 level in nasal lavage from those patients. The IL-8 levels in nasal lavage from patients with nasal polyps were reduced during macrolide treatment. There was significant correlation between decreased IL-8 levels in nasal lavage and the clinical effect of macrolides on the size of the nasal polyps. In the group whose polyps were reduced in size, the IL-8 levels dramatically decreased from 231.2 pg/mL to 44.0 pg/mL (p < 0.05), and were significantly higher before macrolide treatment than those in the group whose polyps showed no change (p < 0.005). This reduction in IL-8 may be an important aspect of the effect of macrolide treatment on nasal polyps in chronic rhinosinusitis.

scholarly journals Increased expression of Toll-like receptor 3 in intrahepatic biliary epithelial cells at sites of ductular reaction in diseased livers

2008 ◽  
Vol 2 (2) ◽  
pp. 222-230 ◽  
Author(s):  
Minoru Nakamura ◽  
Kenji Funami ◽  
Atsumasa Komori ◽  
Terufumi Yokoyama ◽  
Yoshihiro Aiba ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Toll Like Receptor ◽  
Ductular Reaction ◽  
Biliary Epithelial Cells

456 OSTEOPONTIN, A PUTATIVE MARKER FOR DUCTULAR REACTION, IS INDUCED BY JAK/STAT3 ACTIVATION IN HUMAN BILIARY EPITHELIAL CELLS

2008 ◽  
Vol 48 ◽  
pp. S173-S174
Author(s):  
A. Komori ◽  
T. Uemura ◽  
S. Fujiwara ◽  
Y. Aiba ◽  
M. Nakamura ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Ductular Reaction ◽  
Biliary Epithelial Cells ◽  
Putative Marker

Immortalization of male genital duct epithelium: an assay system for the cystic fibrosis gene

1991 ◽  
Vol 98 (1) ◽  
pp. 85-89
Author(s):  
L. Coleman ◽  
A. Harris
Keyword(s):  
Cystic Fibrosis ◽  
Epithelial Cells ◽  
Autosomal Recessive ◽  
Vas Deferens ◽  
Simian Virus 40 ◽  
Simian Virus ◽  
Cystic Fibrosis Gene ◽  
Duct Epithelium ◽  
Male Genital

The epithelia lining the vas deferens and epididymis are directly involved in the pathology of the autosomal recessive disease cystic fibrosis (CF). We have established culture systems for these epithelial cells. Long-term cell lines have now been generated from these primary epithelial cells by transformation with a plasmid containing an origin-defective simian virus 40 (SV40). Lines have been established from vas deferens and epididymis and both maintain expression of the CF gene.

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