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Tricellulin regulates the tight junctions and cytoskeleton of pancreatic acinar cells through the NF‑κB pathway in hypertriglyceridemic acute pancreatitis

  • Authors:
    • Guifang Wei
    • Zhenni Liang
    • Haixing Wei
    • Qing Wu
    • Jie Wang
    • Lianjie Lin
    • Zhihai Liang
    • Huiying Yang
    • Mengbin Qin
  • View Affiliations / Copyright

    Affiliations: Department of Gastroenterology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region 530007, P.R. China, Department of Gastroenterology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region 530021, P.R. China
    Copyright: © Wei et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 87
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    Published online on: May 19, 2026
       https://doi.org/10.3892/br.2026.2160
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Abstract

Hypertriglyceridemic acute pancreatitis (HTGAP) is a clinical emergency. Tight junctions (TJs) and the cytoskeleton are essential for cell‑cell junctions and cell survival, and although tricellulin is a key protein regulating cell junctions, its role in regulating TJ proteins and the cytoskeleton in pancreatic acinar cells in HTGAP is not currently clear. In the present study, 24 female hamsters were assigned to the control, hypertriglyceridemia (HTG), HTGAP and HTGAP + SC75741 groups. HTG was induced by a high‑fat diet and HTGAP was established by retrograde sodium taurocholate injection. Serum triglyceride levels, pancreatic histopathological changes, and pancreatic expression of tricellulin, claudin‑1 and NF‑κB p65 were assessed. Furthermore, AR42J cell models with tricellulin overexpression and knockdown were cultured under HTG conditions, and protein levels were semi‑quantified by western blotting. F‑actin organization was assessed by immunofluorescence staining and intercellular morphology was examined by scanning electron microscopy. The results revealed that tricellulin expression was decreased and p65 expression was increased under hypertriglyceridemic conditions, whereas pancreatic histopathological injury was not significantly increased in the HTG group. The HTGAP group showed significantly more severe pancreatic injury than the control and HTG groups, accompanied by significantly decreased tricellulin and claudin‑1 expression, and significantly increased p65 expression. After SC75741 (an inhibitor of the NF‑κB signaling pathway) treatment, pancreatic injury and p65 expression were significantly decreased, whereas tricellulin and claudin‑1 showed only partial recovery. In AR42J cells, tricellulin overexpression was associated with increased claudin‑1 expression, reduced NF‑κB activation, improved F‑actin organization and better‑preserved intercellular morphology, whereas tricellulin knockdown exhibited the opposite pattern. In conclusion, hypertriglyceridemic conditions were associated with impaired TJ integrity and cytoskeletal disorganization in pancreatic acinar cells, accompanied by reduced tricellulin expression and increased NF‑κB activation. These findings suggest that tricellulin may contribute to HTGAP‑related junctional and cytoskeletal injury, potentially involving NF‑κB signaling.
View Figures

Figure 1

Macroscopic and histopathological
changes in the pancreas of hamsters. (A) Representative macroscopic
appearance of the pancreas in each group. Yellow arrows indicate
the pancreas; red arrows indicate necrotic areas. (B)
Representative hematoxylin and eosin staining of pancreatic tissues
from each group (magnification, x200; scale bars, 100 µm). C,
control; HTG, hypertriglyceridemia; HTGAP, hypertriglyceridemic
acute pancreatitis.

Figure 2

Representative immunohistochemical
staining of tricellulin, claudin-1 and NF-κB p65 in pancreatic
tissues from hamsters in different groups (magnification, x200;
scale bars, 100 µm). C, control; HTG, hypertriglyceridemia; HTGAP,
hypertriglyceridemic acute pancreatitis.

Figure 3

Effects of tricellulin modulation and
NF-κB inhibition on tight junction proteins and NF-κB signaling in
AR42J cells under an HTG environment. (A) Representative western
blot analysis of tricellulin, claudin-1, p-p65, total p65 and
β-actin. Densitometric semi-quantification of (B) tricellulin, (C)
claudin-1 and (D) p-p65 normalized to β-actin or total p65, as
appropriate. Data are presented as the mean ± SD of three
independent biological replicates. ***P<0.001;
****P<0.0001. HTG, hypertriglyceridemia; KD,
knockdown; NC, negative control; OE, overexpression; p-,
phosphorylated.

Figure 4

Representative images of
immunofluorescence analysis of F-actin organization after
tricellulin modulation and SC75741 treatment in AR42J cells.
F-actin is stained with phalloidin (red), and nuclei are stained
with DAPI (blue). White arrows indicate representative areas of
reduced F-actin continuity, weaker cortical distribution and a
disorganized filament pattern. Scale bars, 100 µm. HTG,
hypertriglyceridemia; KD, knockdown; NC, negative control; OE,
overexpression.

Figure 5

Representative images of scanning
electron microscopic analysis of intercellular morphology and
cell-cell contacts in AR42J cells under HTG conditions and SC75741
treatment. White arrows indicate representative changes including
cell swelling, surface irregularity and weakened cell-cell
contacts. Scale bars, 10 µm. HTG, hypertriglyceridemia; KD,
knockdown; NC, negative control; OE, overexpression.
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Copy and paste a formatted citation
Spandidos Publications style
Wei G, Liang Z, Wei H, Wu Q, Wang J, Lin L, Liang Z, Yang H and Qin M: Tricellulin regulates the tight junctions and cytoskeleton of pancreatic acinar cells through the NF‑&kappa;B pathway in hypertriglyceridemic acute pancreatitis. Biomed Rep 25: 87, 2026.
APA
Wei, G., Liang, Z., Wei, H., Wu, Q., Wang, J., Lin, L. ... Qin, M. (2026). Tricellulin regulates the tight junctions and cytoskeleton of pancreatic acinar cells through the NF‑&kappa;B pathway in hypertriglyceridemic acute pancreatitis. Biomedical Reports, 25, 87. https://doi.org/10.3892/br.2026.2160
MLA
Wei, G., Liang, Z., Wei, H., Wu, Q., Wang, J., Lin, L., Liang, Z., Yang, H., Qin, M."Tricellulin regulates the tight junctions and cytoskeleton of pancreatic acinar cells through the NF‑&kappa;B pathway in hypertriglyceridemic acute pancreatitis". Biomedical Reports 25.1 (2026): 87.
Chicago
Wei, G., Liang, Z., Wei, H., Wu, Q., Wang, J., Lin, L., Liang, Z., Yang, H., Qin, M."Tricellulin regulates the tight junctions and cytoskeleton of pancreatic acinar cells through the NF‑&kappa;B pathway in hypertriglyceridemic acute pancreatitis". Biomedical Reports 25, no. 1 (2026): 87. https://doi.org/10.3892/br.2026.2160
Copy and paste a formatted citation
x
Spandidos Publications style
Wei G, Liang Z, Wei H, Wu Q, Wang J, Lin L, Liang Z, Yang H and Qin M: Tricellulin regulates the tight junctions and cytoskeleton of pancreatic acinar cells through the NF‑&kappa;B pathway in hypertriglyceridemic acute pancreatitis. Biomed Rep 25: 87, 2026.
APA
Wei, G., Liang, Z., Wei, H., Wu, Q., Wang, J., Lin, L. ... Qin, M. (2026). Tricellulin regulates the tight junctions and cytoskeleton of pancreatic acinar cells through the NF‑&kappa;B pathway in hypertriglyceridemic acute pancreatitis. Biomedical Reports, 25, 87. https://doi.org/10.3892/br.2026.2160
MLA
Wei, G., Liang, Z., Wei, H., Wu, Q., Wang, J., Lin, L., Liang, Z., Yang, H., Qin, M."Tricellulin regulates the tight junctions and cytoskeleton of pancreatic acinar cells through the NF‑&kappa;B pathway in hypertriglyceridemic acute pancreatitis". Biomedical Reports 25.1 (2026): 87.
Chicago
Wei, G., Liang, Z., Wei, H., Wu, Q., Wang, J., Lin, L., Liang, Z., Yang, H., Qin, M."Tricellulin regulates the tight junctions and cytoskeleton of pancreatic acinar cells through the NF‑&kappa;B pathway in hypertriglyceridemic acute pancreatitis". Biomedical Reports 25, no. 1 (2026): 87. https://doi.org/10.3892/br.2026.2160
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