Immunolocalization of FGF-2, -7, -8, -10 and FGFR-1–4 during regeneration of the rat submandibular gland

Abstract

Fibroblast growth factors (FGFs) and their receptors (FGFRs) play important roles in the development of the submandibular gland. Although regeneration of submandibular glands follows a similar process to their development, it is unknown how FGFs and FGFRs are distributed during regeneration of submandibular gland. The aim of this study was to determine the localization of FGFs and FGFRs during such regenerative processes. After 7 days' obstruction, the submandibular glands were collected at days 0, 1, 3, 7, 11 and 14 after duct release to study regeneration. The regenerative processes of the submandibular gland were investigated by immunohistochemistry for FGF-2, 7, 8, 10 and FGFR-1-4. Immunohistochemical staining revealed that FGF-2 was moderately expressed in the epithelial cells of duct-like structures (DLS) and newly formed acinar cells (NFAC) at days 0-7, and strongly in intercalated duct (ICD) at control gland and Day 7-14. FGF-7 was localized moderately in NFAC and DLS. FGF-8 was localized moderately in the epithelial cells of DLS during regeneration. Strong positive immunoreactions for FGF-10 were found in NFAC and the epithelial cells of DLS during regeneration, as well as the ICD and lateral surfaces of the maturing acinar cells (MAC). FGFR-1 was expressed moderately in the ICD, and weakly in the NFAC and MAC. Positive immunoreactions for FGFR-2 were not observed during regeneration. Additionally, FGFR-4 was detected strongly in the ICD and slightly in NFAC. These findings suggest that FGF-2, -7, -8 and -10 play important roles in NFAC, MAC, and DLS through FGFR-1 and -4 during regeneration of submandibular gland.

Expression of c-kit and Cytokeratin 5 in the Submandibular Gland after Release of Long-Term Ligation of the Main Excretory Duct in Mice

“…Previous studies of the obstruction and release of obstruction of salivary glands have been conducted over approximately 1 week [23, 27, 28]. We chose to examine changes in glandular tissue structure, residual function and regenerative capacity after the release of submandibular gland obstruction in conditions that more closely mimic those encountered in clinical practice.…”

Wound healing after applying a gelatin-based hydrogel sheet to resected rat submandibular gland

“…FGF-2/FGF receptor-1 signaling was found to promote atrophic rat submandibular gland repair [17]. There is a report of localization of FGFs and FGF receptors during atrophic rat submandibular gland regeneration [16], and it has been suggested that epidermal growth factor affects atrophy regeneration [14,15]. However, the process of identifying the function of these growth factors is one of atrophy/regeneration, and no study has evaluated the effect on the necrotic region.…”

“…Immunohistochemical studies of atrophy and regeneration of salivary glands in the above experimental systems revealed localization of growth factors such as epidermal growth factor [14,15], fibroblast growth factors (FGFs) [16], and nerve growth factor [14]. However, their roles remain unclear, and the long-term effects of procedures such as intra-ductal retrograde injection of growth factors are unknown [17].…”

Validation of superior reference genes in mouse submandibular glands under developmental and functional regeneration states

“…Therefore, studies examining novel therapeutic approaches that aim to regenerate the salivary glands and maintain normal salivary secretion are essential for affected patients. Currently, there are three main strategies for restoring salivary gland function: i) The insertion of a therapeutic gene into ductal cells or residual salivary gland acinar cells by retrograde injection of lentivirus as a vector ( 12 ); ii) the activation of stem cell proliferation or differentiation in the gland ( 13 ); and iii) the elucidation of signaling pathways associated with salivary gland regeneration ( 12 ). Among these three approaches, gene therapy allows for the identification of key genes responsible for regulating the regeneration and repair of duct calculus-induced salivary gland fibrosis ( 14 ).…”