Obstructive sleep apnea and rhonchopathy are associated with downregulation of trefoil factor family peptide 3 (TFF3)—Implications of changes in oral mucus composition

Abstract

Study objectivesTrefoil factor family (TFF) peptides belong to the family of mucin-associated peptides and are expressed in most mucosal surfaces. TFF peptides carry out functions such as proliferation and migration enhancement, anti-apoptosis, and wound healing. Moreover, TFFs are associated with mucins and interact with them as “linker peptides”, thereby influencing mucus viscosity.To test the hypothesis that in rhonchopathy and obstructive sleep apnea (OSA) changes occur in the expression of TFF3 and -2 that could contribute to changes in mucus viscosity, leading to an increase in upper airway resistance during breathing.MethodsRT-PCR, Western-blot, immunohistochemistry and ELISA were performed to detect and quantify TFF3 and -2 in uvula samples. In addition, 99 saliva samples from patients with mild, moderate or severe OSA, as well as samples from rhonchopathy patients and from healthy volunteers, were analyzed by ELISA.ResultsTFF3 was detected in all uvula samples. Immunohistochemistry revealed a subjectively decreasing antibody reactivity of the uvula epithelia with increasing disease severity. ELISA demonstrated significantly higher TFF3 saliva protein concentrations in the healthy control group compared to cases with rhonchopathy and OSA. Predisposing factors of OSA such as BMI or age showed no correlation with TFF3. No significant changes were observed with regard to TFF2.ConclusionsThe results suggest the involvement of TFF3 in the pathogenesis of rhonchopathy and OSA and lead to the hypothesis that reduction of TFF3 production by the epithelium and subepithelial mucous glands of the uvula contribute to an increase in breathing resistance due to a change in mucus organization.

Salivary Trefoil Factor Family (TFF) Peptides and Their Roles in Oral and Esophageal Protection: Therapeutic Potential

“…Expression of TFF2 and TFF3 in oral mucosal tissue is downregulated in patients with oral squamous cell carcinoma and oral lichen planus [21,22]. Decreased salivary TFF3 levels were also observed in patients with obstructive sleep apnea and rhonchopathy [23]. Salivary TFF1 and TFF3 concentrations are reduced in patients with chronic periodontitis [24], whereas salivary TFF3 is elevated in children with oral mucositis [25].…”

Different Forms of TFF3 in the Human Saliva: Heterodimerization with IgG Fc Binding Protein (FCGBP)

“…Furthermore, TFF3 is expressed in the oral epithelium and the gingiva [13,16,17,18]. Of note, TFF3 is decreased in patients with chronic periodontitis, oral lichen planus, obstructive sleep apnea, and rhonchopathy [17,18,19].…”

Insights Into Long Non-Coding RNA and mRNA Expression in the Jejunum of Lambs Challenged With Escherichia coli F17

“…Here, we concentrate on two members of TFF family: TFF2 and TFF3 . As previously documented, TFF3 , rather than TFF2 , is more involved in mucosal restitution and protection, especially in intestinal immunity ( 48 ). However, in the present study, TFF2 expression was notably higher in AN lambs than SE lambs (fold change = 204).…”