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Updated: Nov 11, 2025
Seven Steps to Stellate Cells
Published on: May 10, 2011
[Effects of FRNK on activation and migration of hepatic stellate cells]
1Department of Infectious Diseases, Affiliated Hospital of Guizhou Medical University, Guiyang 550004, China.
Insights
Focal adhesion kinase related non kinase (FRNK) inhibits hepatic stellate cell (HSC) activation and migration, crucial processes in liver fibrosis development. This suggests FRNK as a potential therapeutic target for liver fibrosis.
Area of Science:
- Cell Biology
- Gastroenterology
- Biochemistry
Background:
- Hepatic stellate cells (HSCs) play a central role in liver fibrosis.
- Focal adhesion kinase related non kinase (FRNK) is implicated in cellular processes.
- Understanding FRNK's role in HSCs is crucial for developing anti-fibrotic therapies.
Purpose of the Study:
- To investigate the effect of FRNK on the activation and migration of hepatic stellate cells (HSCs).
- To explore the underlying molecular mechanisms involving PY397-FAK, Rac, and Rho activation.
Main Methods:
- Human liver tissues and a carbon tetrachloride-induced mouse liver fibrosis model were used.
- FRNK gene knockout and overexpression models were created.
- Histological staining (HE, Masson), Western blot, and wound healing assays were performed to assess fibrosis, protein expression, and cell migration.
Main Results:
- FRNK expression was lower in fibrotic human liver tissues and FRNK knockout mice showed more severe fibrosis.
- FRNK deficiency or knockout led to increased PY397-FAK, α-SMA, Rac, and Rho activation, enhancing HSC migration.
- FRNK re-expression reversed fibrosis and reduced the activation markers and cell migration.
Conclusions:
- FRNK inhibits HSC activation and migration, thereby ameliorating liver fibrosis.
- The mechanism involves the downregulation of PY397-FAK and the inhibition of Rac and Rho activation.
- FRNK represents a potential therapeutic target for managing liver fibrosis.
Abstract:
Objective: To investigate the effect of focal adhesion kinase related non kinase (FRNK) on the activation and migration of hepatic stellate cells (HSCs). Methods: Human liver tissue was divided into healthy control group and fibrosis group from March 2019 to September 2019 in Affiliated Hospital of Guizhou Medical University. C57BL/6 mice were divided into wild type (WT) and FRNK gene knockout type (FRNK-/-) groups. The liver fibrosis model was established with carbon tetrachloride (CCl4). After that, FRNK gene overexpression (Ad-FRNK) was constructed with adenovirus vector. HE and Masson staining were used to evaluate the pathological changes and fiber deposition of liver tissue. Western blot was used to detect the expression of PY397-FAK and α-SMA protein. Mouse primary HSCs were extracted, and the effect of FRNK on HSCs migration was detected by wound healing, activation of Rac and Rho was detected by Western blot. Results: The expression of PY397-FAK protein in human liver tissue with hepatic fibrosis was significantly higher than that in healthy control group (0.88±0.09 vs. 0.73±0.09). FRNK was significantly lower than that in control group(0.68±0.09 vs. 0.79±0.11). After animal model was set up, the degree of liver fibrosis in FRNK-/-mice (153±13)% was more serious than that in WT (100%) group. The expression of PY397-FAK and α-SMA protein was significantly elevated (2.50±0.23 vs. 0.75±0.09, 1.46±0.20 vs. 0.92±0.10). After FRNK gene was re-expressed (100%), the degree of liver fibrosis was mainly reversed [(74±6)%], and the expression of PY397-FAK and α-SMA was accordingly decreased(0.68±0.11 vs. 1.12±0.19,0.68±0.10 vs. 0.85±0.06). In vitro, FRNK inhibited the migration of HSCs [WT∶FRNK-/-∶Ad-FRNK,(339±49)%∶(580±53)%∶(259±33)%] and the activation of Rac and Rho proteins (Rac: 0.54±0.07 vs. 0.91±0.10 vs. 0.77±0.12,Rho:0.45±0.05 vs. 0.64±0.06 vs. 0.53±0.07), all P<0.01. Conclusions: FRNK can inhibit the activation and migration of HSCs which contributed to liver fibrosis. The potential mechanism is related to down regulation of PY397-FAK and inhibition of Rac and Rho activation.
