Cell death and cell proliferation in the regeneration of atrophied rat submandibular glands after duct ligation

BACKGROUND: The present study aimed to clarify the proliferation and apoptosis of parenchymal cells during regeneration of rat submandibular glands following atrophy. METHODS: Atrophy of the right submandibular gland of rats was induced by excretory duct ligation at the hilum with metal clips, which were removed 1 week (day 0) after ligation. The right submandibular glands were collected from 0 to 14 days after removal of the clips and investigated using immunohistochemistry for proliferating cell nuclear antigen (PCNA) as a marker of proliferating cells, terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-digoxigenin nick end labeling (TUNEL) as a marker of apoptotic cells, and transmission electron microscopy (TEM). RESULTS: After 1 week of ligation, there were many remaining ducts and a few acini in the atrophic glands. At day 3 after discontinuing the ligation, newly formed acini appeared and thereafter increased in number and maturity. Many residual and newly formed acinar cells showed positive reaction to PCNA especially at days 4 and 5. The PCNA-positive duct cells decreased in number with the regeneration. A few TUNEL-positive acinar and duct cells were identified during regeneration. Mitosis and apoptosis of parenchymal cells were also identified by TEM. CONCLUSIONS: During regeneration of the submandibular gland after atrophy, both residual and newly formed acinar cells proliferate actively. There is also apoptosis of parenchymal cells; however, the significance of apoptosis is low.