Keita Tanigaki, Risako Matsumura, Naoko Sasaki, Yuta Kato, Tsukasa Tamamori, Shunsuke Yamaga, Eriko Nakamura, Akito Sakanaka, Masae Kuboniwa, Michiya Matsusaki, Atsuo Amano, Hiroki Takeuchi
Scientific reports 2024 Oct 22Solute carrier family 37 member 4 (SLC37A4) is known to regulate glucose-6-phosphate transport from cytoplasm to the lumen of the endoplasmic reticulum, which serves to maintain glucose homeostasis. Glycogen storage disease type 1b (GSD1b) is caused by a mutation of SLC37A4, leading to a glycogenolysis defect. Although GSD1b cases are known to be complicated by periodontitis, the etiological molecular basis remains unclear. The present study investigated the effects of SLC37A4 on gingival barrier function. Examinations of immortalized human gingival epithelial (IHGE) cells showed SLC37A4 localized in the endoplasmic reticulum. SLC37A4 knockout decreased expression of JAM1, a tight junction-related protein, in IHGE cells. Using in silico analysis to investigate potential transcription factor binding sites, H6 family homeobox 3 (HMX3) was shown to be related to JAM1 expression. In HMX3-knockdown IHGE cells, JAM1 expression was markedly suppressed. Furthermore, HMX3 was scarcely detected in SLC37A4-knockout cells, while HMX3 overexpression restored JAM1 expression in those cells. Finally, using a three-dimensional multilayered gingival epithelial tissue model, knockout of SLC37A4 was also found to increase permeability to lipopolysaccharide and peptidoglycan, which was dependent on JAM1 expression. Specific downregulation of HMX3 by SLC37A4 and the consequent decrease in JAM1 expression provides findings indicating a molecular basis for the reduction in barrier function of gingival epithelial tissues in GSD1b cases. © 2024. The Author(s).
Keita Tanigaki, Risako Matsumura, Naoko Sasaki, Yuta Kato, Tsukasa Tamamori, Shunsuke Yamaga, Eriko Nakamura, Akito Sakanaka, Masae Kuboniwa, Michiya Matsusaki, Atsuo Amano, Hiroki Takeuchi. SLC37A4, gene responsible for glycogen storage disease type 1b, regulates gingival epithelial barrier function via JAM1 expression. Scientific reports. 2024 Oct 22;14(1):24797
PMID: 39433915
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