Reversible Conversion among Subtypes of Salivary Gland Duct Cells as Identified by Production of a Variety of Bioactive Polypeptides

Abstract

Four major kallikreins (mK1, mK22, mK9, and mK13) were identified in the mouse submandibular gland (SMG). mK1, a true tissue kallikrein, was used as a protein marker to identify different types of SMG granular convoluted tubule (GCT) cells along with epidermal growth factor (EGF), nerve growth factor (NGF), and renin. Kallikrein mK1 was localized in a very small number (~5%) of GCT cells, which were scattered throughout the GCT, indicating that the majority of GCT cells are mK1-negative. Among mK1-positive cells, particularly strong signals were observed in a small number of narrow cells, recognized as slender granular cells (SG cells, Type IV), in the GCT. After postnatal development of the SMG, GCT cells are no longer uniform based on the bioactive substances (mK1, EGF, NGF, and renin) that they produce and secrete. GCT cells were classified into four subtypes, Types I–IV, and it became clear that these subtypes are complicatedly and reversibly converted by the endocrine hormones 5α-dihydrotestosterone (DHT) and triiodothyronine (T3). Duct segments with similar morphology or hormone dependency were recognized in the sublingual and parotid glands. The presence of duct cells with such characteristics is therefore a common feature of the three major salivary glands of rodents.

A mesenchymal to epithelial switch in Fgf10 expression specifies an evolutionary-conserved population of ionocytes in salivary glands

“…The shift of FGF10 expression from mesenchymal to epithelial cells is intriguing and observed within a very narrow postnatal time frame. The differentiation of duct cells occurs between 1 and 2 weeks after birth ( Kurabuchi et al, 2019 ), which correlates with the timing of the FGF10 expression shift. Differentiation of GCT cells is normally under hormonal control of androgens (dihydrotestosterone) and possibly other hormones ( Kurabuchi et al, 2019 ; Morrell et al, 1987 ).…”

“…The differentiation of duct cells occurs between 1 and 2 weeks after birth ( Kurabuchi et al, 2019 ), which correlates with the timing of the FGF10 expression shift. Differentiation of GCT cells is normally under hormonal control of androgens (dihydrotestosterone) and possibly other hormones ( Kurabuchi et al, 2019 ; Morrell et al, 1987 ). Mice treated with thyroid hormones and androgens convert SD cells into the GCT-like cells ( Kurabuchi, 2006 ).…”

IFT140+/K14+ cells function as stem/progenitor cells in salivary glands

“…Nerve growth factor (NGF) is produced and stored in the secretory granules by GD cells beginning when mice are 2–3 weeks old. 29 , 30 The staining and quantitative image analysis indicated that NGF contents significantly decreased in the GD cells of Ift140-cKO glands compared with WT (Fig. 5d–f , quantified in m, n), which suggested that granule contents were dysregulated in the absence of IFT140.…”