scholarly journals NCK-associated protein 1 like (nckap1l) minor splice variant regulates intrahepatic biliary network morphogenesis

PLoS Genetics ◽  
2021 ◽  
Vol 17 (3) ◽  
pp. e1009402
Author(s):  
Kimia Ghaffari ◽  
Lain X. Pierce ◽  
Maria Roufaeil ◽  
Isabel Gibson ◽  
Kevin Tae ◽  
...  

Impaired formation of the intrahepatic biliary network leads to cholestatic liver diseases, which are frequently associated with autoimmune disorders. Using a chemical mutagenesis strategy in zebrafish combined with computational network analysis, we screened for novel genes involved in intrahepatic biliary network formation. We positionally cloned a mutation in thenckap1lgene, which encodes a cytoplasmic adaptor protein for the WAVE regulatory complex. The mutation is located in the last exon after the stop codon of the primary splice isoform, only disrupting a previously unannotated minor splice isoform, which indicates that the minor splice isoform is responsible for the intrahepatic biliary network phenotype. CRISPR/Cas9-mediatednckap1ldeletion, which disrupts both the primary and minor isoforms, showed the same defects. In the liver ofnckap1lmutant larvae, WAVE regulatory complex component proteins are degraded specifically in biliary epithelial cells, which line the intrahepatic biliary network, thus disrupting the actin organization of these cells. We further show thatnckap1lgenetically interacts with the Cdk5 pathway in biliary epithelial cells. These data together indicate that althoughnckap1lwas previously considered to be a hematopoietic cell lineage-specific protein, its minor splice isoform acts in biliary epithelial cells to regulate intrahepatic biliary network formation.

2008 ◽  
Vol 173 (2) ◽  
pp. 494-506 ◽  
Author(s):  
Wataru Hashimoto ◽  
Ryo Sudo ◽  
Kazutomo Fukasawa ◽  
Mariko Ikeda ◽  
Toshihiro Mitaka ◽  
...  

2013 ◽  
Vol 58 ◽  
pp. S390
Author(s):  
A. Lleo ◽  
W. Zhang ◽  
W.H. McDonald ◽  
D. Friedman ◽  
E.H. Seeley ◽  
...  

1996 ◽  
Vol 44 (12) ◽  
pp. 1429-1438 ◽  
Author(s):  
A Khoor ◽  
M E Gray ◽  
G Singh ◽  
M T Stahlman

Clara cell-specific 10-KD protein (CCSP) is an abundant product of nonciliated bronchiolar epithelial (Clara) cells in the lung. We have determined the temporal-spatial distribution of CCSP and its mRNA in developing human lung and in neonatal lung disease, using immunohistochemistry and in situ hybridization. CCSP immunoreactivity was found in nonciliated bronchiolar epithelial cells from 12 weeks of gestation onward. Tracheal and bronchial epithelia showed positive immunoreactivity at each gestational week after 15 weeks and 14 weeks, respectively. CCSP mRNA was seen in the bronchial and bronchiolar epithelia from 16 weeks onward and was detected in the trachea from 19 through 23 weeks of gestation. CCSP immunoreactivity and mRNA were present in nonciliated single cells of bronchial and bronchiolar epithelia in fetuses and in infants with and without lung disease. CCSP- and CCSP mRNA-containing epithelial cells also formed dusters around neuroepithelial bodies (NEBs), especially at airway branch points, suggesting that NEBs and Clara cells might interact during development and during pulmonary regeneration. Because of evidence of overlapping of some but not all cells expressing CCSP, SP-A, and pro-SP-B during lung development, a common cell lineage is proposed, with subsequent divergence of phenotypes.


Author(s):  
Odell T. Minick ◽  
Hidejiro Yokoo ◽  
Fawzia Batti

To learn more of the nature and origin of alcoholic hyalin (AH), 15 liver biopsy specimens from patients with alcoholic hepatitis were studied in detail.AH was found not only in hepatocytes but also in ductular cells (Figs. 1 and 2), although in the latter location only rarely. The bulk of AH consisted of a randomly oriented network of closely packed filaments measuring about 150 Å in width. Bundles of filaments smaller in diameter (40-90 Å) were observed along the periphery of the main mass (Fig. 1), often surrounding it in a rim-like fashion. Fine filaments were also found close to the nucleus in both hepatocytes and biliary epithelial cells, the latter even though characteristic AH was not present (Figs. 3 and 4). Dispersed among the larger filaments were glycogen, RNA particles and profiles of endoplasmic reticulum. Dilated cisternae of endoplasmic reticulum were often conspicuous around the periphery of the AH mass. A limiting membrane was not observed.


2021 ◽  
Vol 11 (12) ◽  
pp. 5394
Author(s):  
Jila Nasirzade ◽  
Zahra Kargarpour ◽  
Layla Panahipour ◽  
Reinhard Gruber

Amelotin (AMTN) is a secretory calcium-binding phosphoprotein controlling the adhesion of epithelial cells to the tooth surface, forming a protective seal against the oral cavity. It can be proposed that signals released upon dentinolysis increase AMTN expression in periodontal cells, thereby helping to preserve the protective seal. Support for this assumption comes from our RNA sequencing approach showing that gingival fibroblasts exposed to acid dentin lysates (ADL) greatly increased AMTN expression. In the present study, we confirm that acid dentin lysates significantly increase AMTN in gingival fibroblasts and extend this observation towards the epithelial cell lineage by use of the HSC2 oral squamous and TR146 buccal carcinoma cell lines. AMTN immunostaining revealed an intensive signal in the nucleus of HSC2 cells exposed to acid dentin lysates. Acid dentin lysates mediate their effect via the transforming growth factor (TGF)-β type 1 receptor kinase as the antagonist SB431542 abolished the expression of AMTN in the epithelial cells and fibroblasts. Similar to what is known for fibroblasts, acid dentin lysate increased Smad-3 phosphorylation in HSC2 cells. HSC2 cells also respond to the AMTN-stimulating activity of the dentin lysate when adsorbed to gelatin. When simulating regenerative approaches, enamel matrix derivative, TGF-β1, and bone morphogenetic protein-2 also caused a robust increase in SB431542-dependent AMTN expression in HSC2. Taken together, we show here that acid dentin lysate uses the TGF-β-depended signaling pathway to support the AMTN expression in epithelial cells, possibly helping in maintaining the protective seal against the oral cavity.


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