Have you ever noticed – you have a small wound in your mouth and it healed within a very short time and didn’t leave a scar? This is no coincidence: Wounds in the mouth area usually heal much faster and leave fewer scars than wounds in other skin regions. A research team from Bethesda, USA, investigated this phenomenon using transcriptome analysis.1 Here you can find out what differences have been observed between the oral mucosa and the skin on other parts of the body, and what therapeutic benefit this newly gained knowledge could have, particularly in the case of chronic wounds.1
What exactly was done?
In the clinical study, 30 healthy volunteers were included, in whom on day 1 a 3-mm circular wound was induced using a skin punch on both the inner cheek wall and the inner side of the upper arm. To study the cellular response to the induced wound at the transcriptome level, another 5-mm biopsy was then taken on day 3 and 6, from which RNA could be isolated.1
And what differences did you notice?
In the transcriptome analysis, three points in particular caught the attention of the researchers:1
- Even in the basal state, i.e. before the wound healing begins, transcriptional differences between the oral mucosa and the skin on the upper arm can be observed, which also remain consistent during wound healing.
- Genes associated with wound healing are generally upregulated as a result of the induced wound.
- In contrast to the skin on the upper arm, gene expression in the oral mucosa normalizes as early as day 6.
If you look at the above points in detail, it is noticeable that around 410 genes are significantly deregulated in the oral mucosa by day 3 and by day 6 there are no more genes that are deregulated compared to day 1. In contrast, in the skin on the upper arm, a whopping 1473 genes are deregulated on day 3 and even more genes on day 6 with 1836 genes. But even before the wound occurs, the transcriptome of the two skin areas is different: at baseline, the expression of certain genes in the oral mucosa that are associated with wound healing in keratinocytes is significantly increased. These include keratins 6 (KRT6) and 16 (KRT16), small proline-rich (SPRR) and S100 proteins, defensins, serpins or annexins. This result suggests that the regulatory network of gene expression, which induces the particularly rapid healing mechanisms in the oral mucosa, is already present in the ‘unwounded’ state and does not have to be activated first. True to the motto: Steady, ready, go!1
Does the oral mucosa have a miracle weapon in the event of injuries?
Oh yes, she has! Using a comparative analysis, the researchers were able to find two transcription factors that stand out in the oral mucosa and make a significant contribution to wound healing: there is SOX2 (sex-determining region Y-box 2) and PITX1 (paired-like homeodomain 1). Both factors appear to be responsible for the characteristic network of fast and efficient wound healing in the oral mucosa.1
Can knowledge be used therapeutically?
That is quite conceivable. A mouse model was used to show that wound healing after overexpression of SOX2 was significantly improved compared to the control group (p < 0.05). Histological examinations showed a faster overgrowth of the wound edge as well as significantly more PCNA+ proliferating epithelial cells after SOX2 overexpression in the wound
(p<0.05). Based on these data, it is therefore quite conceivable to treat chronic wounds in particular by means of genetically or pharmacologically induced expression or activity of SOX2 in order to improve wound healing.1
Wounds in the mouth area heal much faster and more efficiently than in other parts of the body. Sometimes a basal basic activity for wound healing in the oral mucosa seems to play a decisive role, in which the transcription factors SOX2 and PITX1 seem to be responsible for this oral mucosa-characteristic network of fast and efficient wound healing. So it is quite conceivable to use a genetically or pharmacologically induced overexpression of SOX2 therapeutically, especially to treat chronic wounds.1
- Iglesias-Bartolome R et al. Sci Transl Med. 2018; 25; 10 (451): eaap8798.