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

Abstract

The present study aimed to clarify the proliferation and apoptosis of parenchymal cells during regeneration of rat submandibular glands following atrophy. 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). 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. 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.