1. Academic Validation
  2. Parasympathetic-macrophages-ductal epithelial cells axis promotes female rat submandibular gland regeneration after excretory duct ligation/deligation

Parasympathetic-macrophages-ductal epithelial cells axis promotes female rat submandibular gland regeneration after excretory duct ligation/deligation

  • Arch Oral Biol. 2023 Jan:145:105586. doi: 10.1016/j.archoralbio.2022.105586.
Bin Wang 1 Dan Li 1 Jing Li 1 Wei An 2 Zhilin Li 3 Qi Shao 4 Lizheng Qin 5
Affiliations

Affiliations

  • 1 Department of Oral and Maxillofacial & Head and Neck Oncology, Beijing Stomatological Hospital, Capital Medical University, Tian Tan Xi Li No.4, Beijing 100050, China.
  • 2 Department of Oral and Maxillofacial Surgery, Shanxi Provincial People's Hospital, Shanxi Medical University, Shuang Ta Si Street No.29, Taiyuan 030012, China.
  • 3 Department of Head and Neck Oncology, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Workers' New Village No.3, Taiyuan 030013, China.
  • 4 Department of Oral and Maxillofacial Surgery, Changsha Stomatological Hospital, You Yi Road No.389, Changsha 410004, China.
  • 5 Department of Oral and Maxillofacial & Head and Neck Oncology, Beijing Stomatological Hospital, Capital Medical University, Tian Tan Xi Li No.4, Beijing 100050, China. Electronic address: [email protected].
Abstract

Objective: Submandibular gland (SMG) regeneration depends on parasympathetic signals that modulate this process primarily by promoting ductal epithelial cell proliferation. The purpose of this study was to elucidate the mechanism underlying of parasympathetic regulation on salivary gland regeneration.

Materials and methods: We performed duct ligation/deligation with or without chorda lingual innervation in female Sprague-Dawley rats. Clodronate liposomes were administered retroductally and intravenously into the SMG to deplete macrophages. The proliferative ability and cell cycle-related genes of SMG were assessed using western blotting, quantitative Real-Time PCR, and immunohistochemical staining.

Results: Parasympathetic stimulation boosted Interleukin-6 (IL-6) release by macrophage via muscarinic signalling. This process was suppressed by denervation, muscarinic blockade, or SMG macrophage depletion. SMG IL-6 release led to signal transducer and activator of transcription 3 (STAT3) phosphorylation in ductal epithelial cells to promote proliferation and regeneration by upregulating the expression of cell cycle-related genes. SMG parasympathetic denervation and macrophage depletion suppressed cell cycle-related genes upregulation and ductal cells proliferation.

Conclusions: These data indicated that the parasympathetic-macrophage-ductal epithelial cells axis promote SMG regeneration after duct ligation and deligation.

Keywords

Interleukin-6; Macrophages; Parasympathetic; Regeneration; Submandibular gland.

Figures
Products