Smad2 is involved in Aggregatibacter actinomycetemcomitans-induced apoptosis

Area of Science:

• Oral biology
• Cellular and molecular biology
• Immunology

Background:

• Apoptosis contributes to periodontitis progression and epithelial barrier dysfunction.
• Smad2 signaling is crucial for apoptosis, but its role in bacteria-induced apoptosis is unclear.
• Periodontopathic bacteria may offer novel therapeutic targets if their apoptosis-inducing mechanisms are understood.

Purpose of the Study:

• To investigate the role of Smad2 phosphorylation in apoptosis of human gingival epithelial cells induced by Aggregatibacter actinomycetemcomitans (Aa).
• To elucidate the signaling pathway involved in Aa-induced apoptosis in gingival epithelial cells.

Main Methods:

• Primary human gingival epithelial cells (HGECs) and OBA9 cells were treated with Aa.
• Smad2 and TGF-β type I receptor (TGF-βRI) phosphorylation were assessed.
• TGF-βRI was inhibited using SB431542 or siRNA.
• Apoptosis and cleaved caspase-3 activation were measured.

Main Results:

• Aa induced Smad2 and TGF-βRI phosphorylation in gingival epithelial cells.
• Inhibition of TGF-βRI attenuated Aa-induced Smad2 phosphorylation.
• Disruption of TGF-βRI signaling abrogated cleaved caspase-3 activation and repressed apoptosis.
• Aa-induced apoptosis in gingival epithelial cells involves the TGF-βRI-Smad2-caspase-3 pathway.

Conclusions:

• Aggregatibacter actinomycetemcomitans (Aa) activates the TGF-βR/Smad2 signaling pathway in human gingival epithelial cells.
• This activation leads to apoptosis of epithelial cells, potentially contributing to periodontitis.
• Targeting this pathway may offer novel therapeutic strategies for periodontitis prevention and treatment.