Activation of GATA‐binding protein 4 regulates monocyte chemoattractant protein‐1 and chemotaxis in periodontal ligament cells

• Published in: Journal of periodontal research 2022-01, Vol.57 (1), p.195-204
• Main Authors: Zhu, Ningjing, Zheng, Xueqing, Qiao, Weiwei, Huang, Wushuang, Li, Ruiqi, Song, Yaling
• Format: Article
• Language: English
• Subjects: Animal models; Animals; Cells, Cultured; Chemokine CCL2 - genetics; Chemokine CCL2 - metabolism; Chemokines; Chemotaxis; Extracellular signal-regulated kinase; GATA4; GATA4 Transcription Factor - metabolism; Gum disease; Immunofluorescence; Immunohistochemistry; Inflammation; Inflammatory diseases; Kinases; Ligaments; Lipopolysaccharides; Macrophages; MAP kinase; MAPK signaling pathways; MCP‐1; Monocyte chemoattractant protein; Monocytes; p38 Mitogen-Activated Protein Kinases - antagonists & inhibitors; p38 Mitogen-Activated Protein Kinases - metabolism; Periodontal ligament; Periodontal Ligament - cytology; Periodontitis; Polymerase chain reaction; Protein kinase; Proteins; Rats; Senescence; Signal transduction; siRNA; Transfection; Western blotting
• ISSN: 0022-3484; 1600-0765
• DOI: 10.1111/jre.12953

Background and Objectives Periodontitis is a chronic inflammatory disease of periodontal supporting tissues. The persistent inflammatory reaction depends on the release of chemokines to continuously recruit inflammation cells. GATA‐binding protein 4 (GATA4) exerts effects on senescence and inflammation, while its role in periodontitis is far from clear. The present study aims to address the effect of GATA4 on regulating chemokines and the chemotaxis in periodontitis. Material and Methods Periodontitis rat models were constructed to detect the expression of GATA4 and the chemokine monocyte chemoattractant protein‐1 (MCP‐1) by immunohistochemistry. Lipopolysaccharide (LPS)‐stimulated human periodontal ligament (PDL) cells and GATA4‐knockdown by siRNA transient transfection PDL cells were used to explore the correlation between GATA4 and chemokines. Transwell assay was performed to detect the role of GATA4 for the recruitment effect of chemokines on macrophages. Mitogen‐activated protein kinase (MAPK) inhibitors were scheduled to intervene in LPS‐stimulated PDL cells to examine the association between MAPK signaling pathways and GATA4. The expression of GATA4, chemokines, or MAPK signaling molecules was determined by quantitative real‐time polymerase chain reaction, western blotting, or cell immunofluorescence. Results The expression of GATA4 and MCP‐1 was significantly increased in periodontitis rat models and in LPS‐stimulated PDL cells. Knockdown GATA4 inhibited the expression of GATA4 and MCP‐1 as well as suppressed the recruitment of macrophage in LPS‐stimulated PDL cells. Inhibitors of p38 and ERK1/2 signaling pathways significantly downregulated the increased expression of GATA4 and MCP‐1 induced by LPS in PDL cells. Conclusions GATA‐binding protein 4 could act as an upstream regulator of MCP‐1 and as a downstream regulator of p38 and ERK1/2 signaling pathways to initiate inflammation response and regulate chemotaxis during the progression of periodontitis.