Woundhealing disorders characterized by impaired or delayed re-epithelialization are a serious medical problem that is painful and difficult to treat. Gelsolin (GSN), a known actin modulator, supports epithelial cell regeneration and apoptosis. The aim of this study was to estimate the potential of recombinant gelsolin (rhu-pGSN) for ocular surface regeneration to establish a novel therapy for delayed or complicated wound healing. We analyzed the influence of gelsolin on cell proliferation and wound healing in vitro, in vivo/ex vivo and by gene knockdown. Gelsolin is expressed in all tested tissues of the ocular system as shown by molecular analysis. The concentration of GSN is significantly increased in tear fluid samples of patients with dry eye disease. rhu-pGSN induces cell proliferation and faster wound healing in vitro as well as in vivo/ex vivo. TGF-β dependent transcription of SMA is significantly decreased after GSN gene knockdown. Gelsolin is an inherent protein of the ocular system and is secreted into the tear fluid. Our results show a positive effect on corneal cell proliferation and wound healing. Furthermore, GSN regulates the synthesis of SMA in myofibroblasts, which establishes GSN as a key protein of TGF-β dependent cell differentiation.

Laryngeal cartilages undergo a slow ossification process during aging, making them an excellent model for studying cartilage mineralization and ossification processes. Pig laryngeal cartilages are similar to their human counterparts in shape and size, also undergo mineralization, facilitating the study of cartilage mineralization. We investigated the processes of cartilage mineralization and ossification and compared these with the known processes in growth plates. Thyroid cartilages from glutaraldehyde-perfused male minipigs and from domestic pigs were used for X-ray, light microscopic, and transmission electron microscopic analyses. We applied different fixation and postfixation solutions to preserve cell shape, proteoglycans, and membranes. In contrast to the ossifying human thyroid cartilage, predominantly cartilage mineralization was observed in minipig and domestic pig thyroid cartilages. The same subset of chondrocytes responsible for growth plate mineralization is also present in thyroid cartilage mineralization. Besides mineralization mediated by matrix vesicles, a second pattern of cartilage mineralization was observed in thyroid cartilage only. Here, the formation and growth of crystals were closely related to collagen fibrils, which served as guide rails for the expansion of mineralization. It is hypothesized that the second pattern of cartilage mineralization may be similar to a maturation of mineralized cartilage after initial matrix vesicles-mediated cartilage mineralization.

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.