P75NTR promotes radiation-induced submandibular gland epithelial cell apoptosis via the ceramide signaling

  • Arch Oral Biol. 2026 Aug:188:106607. doi: 10.1016/j.archoralbio.2026.106607.
Shen-Sui Li  1 ,  Xu-Dong Tian  2 ,  Ju-Kun Song  3 ,  Ya-Dong Wu  4 ,  Wei-Li Wang  5 ,  Zheng-Long Tang  6
Affiliations
  • 1. College of Stomatology, Guizhou Medical University, China; Department of Oral and Maxillofacial Surgery, the Affiliated Stomatological Hospital of Guizhou Medical University, No. 9, Beijing Road, Yunyan District, Guiyang City, Guizhou Province 550004, China. Electronic address: [email protected].
  • 2. College of Stomatology, Guizhou Medical University, China; Department of Oral and Maxillofacial Surgery, the Affiliated Stomatological Hospital of Guizhou Medical University, No. 9, Beijing Road, Yunyan District, Guiyang City, Guizhou Province 550004, China. Electronic address: [email protected].
  • 3. College of Stomatology, Guizhou Medical University, China; Department of Oral and Maxillofacial Surgery, the Affiliated Stomatological Hospital of Guizhou Medical University, No. 9, Beijing Road, Yunyan District, Guiyang City, Guizhou Province 550004, China. Electronic address: [email protected].
  • 4. College of Stomatology, Guizhou Medical University, China; Department of Oral and Maxillofacial Surgery, the Affiliated Stomatological Hospital of Guizhou Medical University, No. 9, Beijing Road, Yunyan District, Guiyang City, Guizhou Province 550004, China. Electronic address: [email protected].
  • 5. Department of Hematology, the Affiliated Hospital of Guizhou Medical University, No. 28, Guiyi Street, Yunyan District, Guiyang City, Guizhou Province 550004, China. Electronic address: [email protected].
  • 6. College of Stomatology, Guizhou Medical University, China; Department of Oral and Maxillofacial Surgery, the Affiliated Stomatological Hospital of Guizhou Medical University, No. 9, Beijing Road, Yunyan District, Guiyang City, Guizhou Province 550004, China. Electronic address: [email protected].
PMID: 42134022 DOI: 10.1016/j.archoralbio.2026.106607
Abstract

Objective: Radiotherapy for head and neck cancers often damages normal tissues, including radiation-induced sialadenitis. The role of the p75 neurotrophin receptor (p75NTR) in radiation injury is dual; however, its mechanisms in salivary glands are unclear. This study examines p75NTR's role in radiation-induced submandibular gland injury.

Design: Acinar-like human salivary gland epithelial cells (HSG-AZA3) were irradiated after p75NTR overexpression (oe-p75NTR) or knockdown (sh-p75NTR). We assessed Apoptosis, ceramide levels, oxidative stress, inflammatory factors, and apoptosis-related gene/protein expression. Additionally, we explored the impact of sh-p75NTR combined with the Ceramidase Inhibitor (Ceranib2) on irradiated HSG-AZA3 cells. Animal experiments evaluated the effects of sh-p75NTR and Ceranib2 on radiation damage to mouse mandibular glands.

Results: Oe-p75NTR increased radiation-induced oxidative stress, inflammatory responses, and Apoptosis, whereas sh-p75NTR offered protection by reducing these effects. Ceranib2 reversed sh-p75NTR's protective effects, increasing ceramide levels, oxidative stress, and Apoptosis. In mice, sh-p75NTR protected against radiation-induced gland injury, while Ceranib2 diminished this protection and increased damage.

Conclusions: Interfering with p75NTR provides protection against radiation-induced salivary gland cell injury, while Ceranib2 negates this by boosting ceramide levels and promoting Apoptosis. These findings suggest new molecular pathways involved in radiation-induced salivary gland injury and potential targets for developing radiation protection strategies.

Keywords
Ceramide; P75NTR; Radiation; Salivary gland.
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