Regeneration of the Salivary Glands after Transient Immune-mediated Injury is Dependent on the Cell Cycle Promoter aurora kinase B.

Objectives:
How secretory cells are replaced following salivary gland (SG) injury remains unclear. In the present study, a novel mouse model featuring SG injury and regeneration was used to investigate the mechanisms underlying replenishment of the glandular cells after severe but transient ablation.
Methods:
Experiments on mice were conducted under licence with permission of the King's College London Animal Welfare & Ethical Review Body. Mouse (C57BL/6) submandibular glands (SMGs) were challenged with poly I:C for the induction of transient TLR-3-mediated injury.The acute damage and regeneration phases were comprehensively characterized by assessing secretory function, histomorphology and gene expression. The cell cycle promoter aurora kinase B (AURKB) was inhibited using the highly potent and selective inhibitor Barasertib (AZD1152-HQPA), in order to investigate the mechanisms that controlled cellular cycling and proliferation during SMG regeneration.
Results:
Activation of TLR-3 induced a loss and regain of saliva secretion during a 14 day period as previously described (Shaalan et al., 2018, J. Oral Pathol. Med. 47, 211-9). In parallel there was apoptotic depletion of the acinar (Mist1 positive) cell compartment followed by rapid repopulation with acinar cells. Dramatic declines in the neuronal, ductal and putative progenitor cell repertoires, were followed by rapid expansion. Importantly, the cell cycle promoter AURKB, was transiently elevated during the regeneration phase and was essential for functional restoration and cellular replenishment of Mist1-positive acinar cells after acute injury and depletion.
Conclusions: Adult murine salivary glands regenerate after severe, acute injury. Functional and morphological restoration of acinar cells is dependent upon upregulated expression of the serine/ threonine kinase, aurora kinase B.