Abstract
Oral mucosal wounds are characterized by rapid healing with minimal scarring, partly attributable to the “enhanced” wound healing properties of oral mucosal fibroblasts (OMFs). Hepatocyte growth factor (HGF) is a pleiotropic growth factor, with potential key roles in accelerating healing and preventing fibrosis. HGF can exist as full-length or truncated (HGF-NK), NK1 and NK2 isoforms. As OMFs display elevated HGF expression compared to dermal fibroblasts (DFs), this study investigated the extent to which HGF mediates the preferential cellular functions of OMFs, and the influence of pro-fibrotic, transforming growth factor-β1 (TGF-β1) on these responses. Knockdown of HGF expression in OMFs by short-interfering RNA (siHGF) significantly inhibited OMF proliferative and migratory responses. Supplementation with exogenous TGF-β1 also significantly inhibited proliferation and migration, concomitant with significantly down-regulated HGF expression. In addition, knockdown abrogated OMF resistance to TGF-β1-driven myofibroblast differentiation, as evidenced by increased α-smooth muscle actin (α-SMA) expression, F-actin reorganisation, and stress fibre formation. Responses were unaffected in siHGF-transfected DFs. OMFs expressed significantly higher full-length HGF and NK1 levels compared to patient-matched DFs, whilst NK2 expression was similar in both OMFs and DFs. Furthermore, NK2 was preferentially expressed over NK1 in DFs. TGF-β1 supplementation significantly down-regulated full-length HGF and NK1 expression by OMFs, while NK2 was less affected. This study demonstrates the importance of HGF in mediating “enhanced” OMF cellular function. We also propose that full-length HGF and HGF-NK1 convey desirable wound healing properties, whilst fibroblasts preferentially expressing more HGF-NK2 readily undergo TGF-β1-driven differentiation into myofibroblasts.
Highlights
Wound healing is a complex and highly ordered chain of events that leads to tissue repair
Here, we show for the first time that as with proliferative and migratory responses, Oral mucosal fibroblasts (OMFs) resistance to transforming growth factor-β1 (TGF-β1)-driven fibroblast-myofibroblast differentiation was significantly impaired by exogenous TGF-β1 supplementation following Hepatocyte growth factor (HGF) knockdown
The findings from this study suggest the beneficial cellular functions of OMFs, required for their impeccable ability to heal oral mucosal tissue, was primarily attributed to the high levels of HGF synthesised by these cells
Summary
Wound healing is a complex and highly ordered chain of events that leads to tissue repair. Oral mucosal and dermal wounds proceed through similar stages of healing, oral mucosal wounds, in common with early-gestational foetal wounds [1], are characterized by minimal inflammatory and angiogenic responses, rapid healing/remodelling, and minimal scar formation. This is in contrast to adult dermal wounds, which are usually accompanied by prominent scar formation [2,3]. Oral mucosal healing is a consequence of phenotypic differences between the intra- and extra-oral wound cell populations. The different responses to exogenous TGF-β1 treatment in DFs and OMFs are thought to be a consequence of differential Smad and hyaluronan regulation [15]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
