Does Adult Rat Submandibular Gland Regeneration Follow the Embryonic/Perinatal Pathway?

Introduction: adult submandibular glands can regenerate following ligation-induced atrophy, but how this process takes place is still unclear. Proliferation of surviving differentiated cells and/or differentiation of pluripotent cell precursors may contribute to repopulate the gland. We provide preliminary evidence of parenchyma regeneration via the embryonic pathway of glandular development. Objective: to identify similarities between regeneration and the embryonic pathway of cytodifferentiation. Methods: in 8 male rats (Wistar) atrophy was induced, under recovery anaesthesia, by applying a metal clip on the main duct of submandibular gland. After 2 weeks the duct was deligated for 5 or 7 days, and then the glands were collected. Tissue was fixed for histological analysis, some used for RNA extraction and some for biochemistry. Tissues from 2 unoperated rats were used as a control. Results: regenerating tissue revealed numerous novel branched structures. These structures, not normally seen in adult, are characterized by a branched duct with at least 3 ramifications each ending with mature or immature acini. Actin immunohistochemistry showed that some of these structures were surrounded by myoepithelial cells, however, the majority of them exhibit immunoreactivity only around the extremities. The perinatal protein SMG-B is localized in the pro-acinar cell during development while in the adult it localizes in the intercalated duct. Here preliminary data revealed a progressive increase in the expression of this protein across our time points. Interesting SMG-B seems to localize in the new acini and in the immature acini at the extremities of the branched structures, whilst the ducts appeared negative. Conclusions: we show preliminary evidence of a correlation between the glandular regeneration and the embryonic pathway of development. Our data suggest that another mechanism, different from proliferation of surviving cells, is also involved in the glandular regeneration.

We gratefully acknowledge Wellcome Trust funding.