2. Academic Validation
  3. Tcf21 Alleviates Pancreatic Fibrosis by Regulating the Epithelial-Mesenchymal Transformation of Pancreatic Stellate Cells

Tcf21 Alleviates Pancreatic Fibrosis by Regulating the Epithelial-Mesenchymal Transformation of Pancreatic Stellate Cells

  • Dig Dis Sci. 2023 Mar 21. doi: 10.1007/s10620-023-07849-w.
Yan-Hong Ni # 1 2,  Rong Wang # 1 2 3 4,  Wen Wang # 1 2 3 4,  Da-Zhou Li # 1 2 3 4,  Gang Liu 1 2 3 4,  Chuan-Shen Jiang 1 2 3 4,  Yi Wang 1 2,  Xia Lin 3,  Xiang-Peng Zeng 5 6 7 8
Affiliations

Affiliations

  • 1 Department of Digestive Diseases, 900TH Hospital of Joint Logistics Support Force, Fujian University of Traditional Chinese Medicine, Fuzhou, China.
  • 2 College of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, China.
  • 3 Department of Digestive Diseases, Fuzong Clinical Medical College, Fujian Medical University, 156 North Road of West No.2 Ring, Fuzhou, 350025, China.
  • 4 Department of Digestive Diseases, Dongfang Hospital, Xiamen University, Fuzhou, China.
  • 5 Department of Digestive Diseases, 900TH Hospital of Joint Logistics Support Force, Fujian University of Traditional Chinese Medicine, Fuzhou, China. doctorzxp@fjmu.edu.cn.
  • 6 College of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, China. doctorzxp@fjmu.edu.cn.
  • 7 Department of Digestive Diseases, Fuzong Clinical Medical College, Fujian Medical University, 156 North Road of West No.2 Ring, Fuzhou, 350025, China. doctorzxp@fjmu.edu.cn.
  • 8 Department of Digestive Diseases, Dongfang Hospital, Xiamen University, Fuzhou, China. doctorzxp@fjmu.edu.cn.
  • # Contributed equally.
PMID: 36943591 DOI: 10.1007/s10620-023-07849-w
Abstract

Background and aims: The activation of pancreatic stellate cells (PSCs) plays a key role in the occurrence and development of chronic pancreatitis (CP) and pancreatic fibrosis, which is related to the process of epithelial-mesenchymal transition (EMT). This study was designed to investigate the effect and mechanism of Tcf21 (one of tumor suppressor genes) on pancreatic inflammation and fibrosis in vivo and in vitro.

Methods: C57BL/6 male mice were intraperitoneally injected with caerulein for 6 weeks to establish CP animal model. Fixed pancreatic tissue paraffin-embedded sections were used for immunohistochemistry staining of Tcf21, fibrosis-related markers (α-SMA), interstitial markers (Vimentin) and epithelial markers (E-cadherin). Western blotting and qRT-PCR assay were performed to analyze the change of expression of the above markers after stimulation of TGF-β1 or overexpressed Tcf21 lentivirus transfection in human pancreatic stellate cells (HPSCs).

Results: The pancreatic expression of α-SMA and Vimentin of CP mice significantly increased, while the expression of Tcf21 and E-cadherin significantly decreased. TGF-β1 could promote activation and EMT process of HPSCs, and inhibited the expression of Tcf21. Overexpression of Tcf21 could significantly down-regulate the expression of α-SMA, Fibronectin and Vimentin, and up-regulated the expression of ZO-1 of HPSCs. Cell Counting Kit-8 assay and scratch wound-healing assay results showed that overexpression of Tcf21 could significantly inhibit the cell migration and proliferation of HPSCs.

Conclusions: Overexpression of Tcf21 could significantly alleviate the activation, proliferation, migration of PSCs by regulating the EMT process. Tcf21 had a potential prospect of a new target for CP therapy.

Keywords

Chronic pancreatitis; Epithelial-mesenchymal transition; Pancreatic fibrosis; Pancreatic stellate cells; Transcription factor 21.

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