Major salivary glands of both humans and rodents consist of three pairs of macroscopic glands: parotid, submandibular, and sublingual. These glands secrete serous, mucous or mixed saliva via the proper main excretory ducts connecting the glandular bodies with the oral cavity. A series of discoveries about the salivary ducts in the 17th century by Niels Stensen (1638–1686), Thomas Wharton (1614–1673), and Caspar Bartholin (1655–1738) established the concept of exocrine secretion as well as salivary glands. Recent investigations have revealed the endocrine functions of parotin and a variety of cell growth factors produced by salivary glands. The present review aims to describe macroscopic findings on the major salivary glands of rodents and the microscopic differences between those of humans and rodents, which review should be of interest to those researchers studying salivary glands.
The process of saliva production in the salivary glands requires transepithelial water transfer from the interstitium to the acinar lumen. There are two transepithelial pathways: the transcellular and paracellular. In the transcellular pathway, the aquaporin water channels induce passive water diffusion across the membrane lipid bilayer. It is well known that aquaporin-5 (AQP5) is expressed in the salivary glands, in which it is mainly localized at the apical membrane of the acinar cells. This suggests the physiological importance of AQP5 in transcellular water transfer. Reduced saliva secretion under pilocarpine stimulation in AQP5-null mice compared with normal mice further indicates the importance of AQP5 in this process, at least in stimulated saliva secretion. Questions remain therefore regarding the role and importance of AQP5 in basal saliva secretion. It has been speculated that there would be some short-term regulation of AQP5 such as a trafficking mechanism to regulate saliva secretion. However, no histochemical evidence of AQP5-trafficking has been found, although some of biochemical analyses suggested that it may occur. There are no reports of human disease caused by AQP5 mutations, but some studies have revealed an abnormal subcellular distribution of AQP5 in patients or animals with xerostomia caused by Sjögren’s syndrome and X-irradiation. These findings suggest the possible pathophysiological importance of AQP5 in the salivary glands.
The nerve growth factor (NGF) family comprises NGF, brain-derived neurotrophic factor (BDNF) and neurotrophins (NTs)-3, -4/5, -6 and -7, all of which are collectively referred to as neurotrophins. However, the expression of neurotrophins other than NGF in the salivary gland has not been described in detail. Through interaction with the TrkB receptor, BDNF plays an important role in long-term potentiation. We found that BDNF expression increased within submandibular gland tissue in response to stress, suggesting that the salivary glands are sensitive to stress. In addition, stress caused increases in plasma BDNF derived from the submandibular gland and in TrkB receptor mRNA in the adrenal medulla. Plasma BDNF might activate TrkB receptors in the adrenal medulla during acute stress. The salivary glands are likely to influence not only oral health, but also systemic organs. This review addressed the relationship between hormone-like effects and stress-related BDNF expression in the rat submandibular gland.
Salivary gland tumors are relatively uncommon and there exists a considerable diagnostic difficulty owing to their diverse histological features in individual lesions and the presence of a number of types and variants, in addition to overlapping histological patterns similar to those observed in different tumor entities. The classification is complex, but is closely relevant to the prognostic and therapeutic aspects. Although hematoxylin-eosin staining is still the gold standard method used for the diagnosis, immunohistochemistry (IHC) can enhance the accuracy and be a helpful tool when in cases to investigate the subjects that cannot be assessed by histological examination, such as the cell nature and differentiation status, cell proliferation, and tumor protein expression. This review depicts on the practical diagnostic utility of IHC in salivary gland tumor pathology under the following issues: assessment of cell differentiation, focusing on neoplastic myoepithelial cells; discrimination of histologically mimic tumor groups; diagnosis of specific tumor types, e.g., pleomorphic adenoma, adenoid cystic carcinoma, and salivary duct carcinoma; and evaluation of malignancy and prognostic factors. IHC plays a limited, even though important, role in the diagnosis of salivary gland tumors, but is often useful to support the histological assessment. However, unfortunately few tumor type-specific markers are still currently available. For these reasons, IHC should be considered a method that can be used to assist the final diagnosis, and its results themselves do not directly indicate a definitive diagnosis.
The aim of this study was to evaluate the influence of mechanical unloading on the repair of bone defects with implantation of biodegradable bone substitutes. Spherical granules of biodegradable hydroxyapatite composed of rod-shaped particles (RHA) or beta-tricalcium phosphate composed of rod-shaped particles (RTCP) were implanted into a bone defect created in the distal end of the right femur of 8-week-old Wistar rats. Two, 6, 10, and 22 weeks after implantation, part of the sciatic nerve in the thigh was resected and exposed to mechanical unloading for 2 weeks. Then, 4, 8, 12 and 24 weeks after implantation, repair of the bone defect was analyzed. As a control, the bone defect without implantation of ceramic granules was also analyzed. Both RHA and RTCP tended to be reduced, but the reduction was not obvious during the experimental period. At 12 and 24 weeks after implantation, the amount of newly formed bone in the animal implanted with RHA was significantly greater than that at 4 weeks after implantation, but that in the animal implanted with RTCP or without implantation was not significantly different. The number of osteoclasts in the region implanted with RHA was significantly larger than that of the region implanted with RTCP or without implantation at 12 and 24 weeks. The activities of alkaline phosphatase in osteoblasts and tartrate-resistant acid phosphatase in osteoclasts were remarkably increased in the bone defects with implantation compared with those in the bone defects without implantation. These results suggested that RHA stimulated osteogenesis and osteoclastogenesis even after 2 weeks of mechanical unloading, and that RHA could be expected to improve the repair of bone defects in patients under the condition of skeletal unloading.
The CXCR4/CXCL12 pathway has recently been reported to be involved in stimulating the metastasis of many different neoplasms, in which CXCR4 activates various phenomena such as chemotaxis, invasion, angiogenesis and proliferation. The purpose of this study was to analyze a possible association between the expression of chemokine receptors CXCR4, CCR6 and CCR7 with the clinicopathological features of cutaneous malignant melanoma, and to assess the usefulness of these chemokine receptors for diagnosis and prognosis. In our study, a percentage of immunoexpression of both CXCR4 and its ligands CXCL12 was associated with high clinical risk. In contrast, the patients with a low immunoexpression of CXCR4 and CXCL12 had low clinical risk. CCR6 and CCR7 immunoexpressions were also correlated with some clinical parameters, but seemed no more useful than CXCR4. These data suggest that the assessment of CXCR4 immunoexpression is a novel tool for predicting tumor aggressiveness in malignant melanomas, and in particular, a high immunoexpression percentage of CXCR4 and CXCL12 might be a sign of a poor prognosis.
The presence of cytoplasmic sialyl glycoproteins is a conspicuous feature in chromophobe renal cell carcinoma (RCC). We compared the immunohistochemical expression of sialyl glycoproteins in chromophobe RCC with that in other types of renal tumors. Formalin-fixed, paraffin-embedded tissues of surgically resected renal tumors (chromophobe RCC, 14 cases [10 cases of classic type and 4 cases of eosinophilic variant]; oncocytoma, 7 cases; and clear cell RCC, 9 cases) and kidneys from immature infants (4 cases) were immunostained with antibodies against sialyl glycoproteins (anti-KL-6 and anti-sialyl MUC1 antibodies). Cytoplasmic expression of KL-6 and sialyl MUC1 was distinctive in the chromophobe RCC and renal oncocytoma cells, and in the intercalated cells in collecting duct epithelia. Apical-surface staining of these sialyl glycoproteins was predominantly observed in clear RCC, in the epithelia of the distal tubule and collecting duct, and in the neonatal renal proximal tubule, but not in those of the adult renal proximal tubule. The above-mentioned observations provide additional evidence for similar phenotypic profiles of chromophobe RCC and renal oncocytoma, and the intercalated cells in collecting ducts and the oncofetal expression of sialyl glycoproteins in clear cell RCC. KL-6 is a potential tumor marker for renal tumors.
Laminin is a key component of the basement membrane and is involved in the structural scaffold and in cell proliferation and differentiation. Research has identified 19 laminin isoforms, which are assemblies of α, β, and γ chains (eg, the α1, β1, and γ1 chains form the laminin 111 isoform). Although laminin is known to be present in the anterior pituitary, the specific laminin isoforms have not been identified. This study used molecular biological and histochemical techniques—namely, RT-PCR, immunohistochemistry, and in situ hybridization—to identify the laminin isoforms and laminin-producing cells in rat anterior pituitary. RT-PCR showed that laminin α1, α3, and α4 genes were expressed in anterior pituitary. Immunohistochemistry revealed laminin α1 in gonadotrophs and laminin α4 in almost all vascular endothelial cells. Laminin α3 was seen in a subset of vascular endothelial cells. We then performed in situ hybridization to localize β and γ chains in these cells and found that laminin β1, β2, and γ1 were expressed in gonadotrophs and that laminin β1 and γ1 were expressed in endothelial cells. In conclusion, we identified gonadotroph-type (laminin 111 and 121) and vascular-type (laminin 411 and 311) laminin isoforms in rat anterior pituitary.