Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0043352 (xerostomia)
 4,250 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Parasympathectomy leads to retrogressive alteration and dysfunction of the submandibular gland (SMG) within 1 month, but its long-term effect is unclear. Excessive secretion is observed in half of the patients 4-6 months after SMG transplantation, which completely denervates the gland. Here, we investigated the long-term effect of parasympathectomy on the secretion of SMGs in minipigs. The results showed that the resting salivary secretion of SMGs decreased by 82.9% of that in control at 2 months after denervation, but increased by 156% at 6 months. Although experiencing an atrophic period, the denervated glands regained their normal morphology by 6 months. The expression of the function-related proteins, including muscarinic acetylcholine receptor (mAChR) 3, aquaporin 5 (AQP5), tight junction protein claudin-3, and claudin-4 was decreased at 2 months after denervation. Meanwhile, the protein expression of stem cell markers, including sex-determining region Y-box 2 and octamer-binding transcription factor 4, and the number of Ki67+ cells were significantly increased. However, at 6 months after denervation, the expression of mAChR3, AQP5, claudin-1, claudin-3, and claudin-4 was significantly raised, and the membrane distribution of these proteins was increased accordingly. The autonomic axonal area of the glands was reduced at 2 months after denervation but returned to the control level at 6 months, suggesting that reinnervation took place in the long term. In summary, parasympathectomy increases resting secretion of the SMGs in the long term with a possible mechanism involving improved transepithelial fluid transport. This finding may provide a new strategy for xerostomia treatment.
 ...
PMID:Parasympathectomy increases resting secretion of the submandibular gland in minipigs in the long term. 3038 29

IgG4-related sialadenitis (IgG4-RS) is a chronic fibro-inflammatory disease characterized by swelling of salivary glands and varying degrees of xerostomia. Tight junctions (TJs) play an essential role in maintaining secretory function by regulating the paracellular flow of ions and water. However, whether TJs are altered and contribute to the hyposecretion in IgG4-RS is not fully understood. Here, a total of 399 differentially expressed proteins were identified in IgG4-RS submandibular glands (SMGs) and enriched in the regulation of actin cytoskeleton and the salivary secretion. Real-time PCR results showed that the mRNA levels of claudin-3, -4, -6, -7, -8, -10, -12, occludin, and ZO-1 were significantly lower, whereas claudin-1 and -5 were higher in IgG4-RS SMGs. Immunohistochemical and immunofluorescence staining revealed that claudin-1, -3, -4, occludin, and ZO-1 were mainly distributed at apicolateral membranes in acini and ducts of SMGs from controls, whereas claudin-1 protein intensity at apicolateral membrane was elevated, while the staining of claudin-3, -4, and ZO-1 were reduced in IgG4-RS SMGs. Occludin was dispersed into cytoplasm of acini and ducts in SMGs of patients. Among them, claudin-3 and ZO-1 protein levels were positively correlated with saliva flow rate. Furthermore, the decreased fluorescence intensity of F-actin at peri-apicolateral membranes and the loss of ZO-1 staining at the same location were observed in acinar and ductal cells of IgG4-RS SMGs, which might be responsible for disorganization of TJ complex. Taken together, these findings indicate that the integrity of TJ complex of SMGs is impaired and might contribute to hyposalivation of IgG4-RS patients.
 ...
PMID:Disruption of tight junction structure contributes to secretory dysfunction in IgG4-related sialadenitis. 3186 2