CCCTC-binding factor transcriptionally regulates Galectin-7 and activates the JNK/STAT3 axis to aggravate bronchial epithelial cell injury.

Abstract

OBJECTIVE:

Studies have shown that the expression of CCCTC-binding factor (CTCF) is significantly upregulated in the airway epithelial cells of asthmatic patients, suggesting that CTCF may play an important role in the progression of asthma.

MATERIAL/METHODS:

Human bronchial epithelial cells BEAS-2B were stimulated with transforming growth factor-β1 (TGF-β1) at a concentration of 10 ng/ml, and CTCF overexpression plasmid and CTCF small interfering RNA were transfected into the cells. The proliferation, apoptosis, inflammatory factor secretion, and airway remodeling marker protein expression of injured cells were detected. We bidirectionally regulated Galectin-7 expression in TGF-β1-induced BEAS-2B cells and overexpress CTCF, while interfering with Galectin-7 to further explore the regulatory effect of CTCF on Galectin-7. We introduced SP600125, a c-Jun N-terminal kinase c-Jun (JNK) pathway inhibitor, to investigate whether CTCF affects asthma progression through the JNK pathway.

RESULTS:

The expression of CTCF in BEAS-2B cells induced by TGF-β1 was significantly upregulated, interfering with CTCF expression promoted cell proliferation, inhibited apoptosis, reduced inflammatory factors secretion, and decreased the expression of airway remodeling marker protein. Luciferase reporter gene analysis and chromatin immunoprecipitation verified that CTCF directly bound to Galectin-7 promoter. The effect of Galectin-7 on cells is consistent with the effect of CTCF on cells. The regulatory effect of CTCF on injured cells was indeed mediated by activation of the JNK/STAT3 axis.

CONCLUSIONS:

CTCF transcriptionally regulated Galectin-7 and activated JNK/STAT3 axis to aggravate bronchial epithelial cell injury.

• Authors: Xinrong Sun, Wenna Shen, Zhaokun Li, Wanggang Zhang
• Journal: Pediatric pulmonology (Pediatr Pulmonol) Vol. 57 Issue 1 Pg. 90-99 (01 2022) ISSN: 1099-0496 [Electronic] United States
• PMID: 34643340 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 Wiley Periodicals LLC.

Chemical References

• CCCTC-Binding Factor
• CTCF protein, human
• Galectins
• LGALS7 protein, human
• STAT3 Transcription Factor
• STAT3 protein, human
• Transforming Growth Factor beta1

Topics

• Asthma (genetics)
• CCCTC-Binding Factor
• Cell Line
• Epithelial Cells (metabolism)
• Galectins
• Humans
• MAP Kinase Signaling System
• STAT3 Transcription Factor
• Transforming Growth Factor beta1 (genetics, metabolism)