In August, the front cover of JID (Journal of Investigative Dermatology) displayed an image of the three-dimensional structure of a skin protease, and the September issue had immunofluorescence photos showing the location of transglutaminases in hair. While it is not surprising that photographs of proteins expressed in the skin and hair should be displayed on the front page of an international journal for research into skin biology, the facts that they came from two publications of L'Oreal research and that all these proteins are involved in epidermal differentiation are not only worth noting but also deserving of a few words of explanation.
Epidermal differentiation: this is a key stage in the establishment of the skin's barrier function and hair shaft formation.
The stratum corneum, the outermost layer of the skin and the part that provides a barrier between our bodies and the external environment, and the hair shaft, the part of the hair follicle that emerges from the skin to provide us with our head of hair, represent in both cases the culmination of the process of keratinocyte differentiation. Several families of proteins play an active part in the various phases of differentiation, each with a specific role to play. Among these, the proteases are fundamental to desquamation, or the elimination of corneocytes from the surface of the epidermis, and the transglutaminases play a part in the reticulation of the proteins that will form the horny outer layer of the skin and the hair shaft.
A new aspartic acid protease specifically identified in the skin
SASPase - short for Skin ASpartic Protease - is a protease expressed specifically in the granular layer of the human epidermis. The identification of this protein in late-phase epidermal differentiation is a first - it had never been previously described.
The discovery and nature of this protein was a source of many surprises for researchers. Dominique Bernard, manager of the "Skin and Surface Aspects" section in Life Sciences points out: "We were surprised first of all to discover a new protein in the epidermis that plays a part in desquamation and then to find that the protease could be an unwanted target of antiviral treatments". This is because the nucleotide sequence of this protease is very similar to that of retroviruses and one of the questions currently being asked is whether it might be that at some time in the past the human genome captured and integrated the gene of the retroviral protease or whether on the reverse could be true, that a retrovirus assimilated this ancestral human protease into its own genome.
The similarity between the human and retroviral protease sequences would provide an explanation of the side effects for the skin of antiviral treatments, especially Indinavir (an HIV protease inhibitor): the skin dryness and hair loss observed during treatment could in fact be linked to the destruction of this protease in the patient's epidermis.
The team is now seeking to modulate the expression of this protease whose function is probably to help establish the barrier function of the epidermis.
D. Bernard*, B. Méhul, A. Thomas-Collignon*, C. Delattre*, M. Donovan* and R. Schmidt*. Identification and Characterization of a Novel Retroviral-Like Aspartic Protease Specifically Expressed in Human Epidermis. The Journal of Investigative Dermatology125 (2), 278-287
Expression of Transglutaminase 5 in the human hair follicle
* L'Oréal Recherche
While Transglutaminase (TG) 5 had been identified very recently in the epidermis by researchers at the University of Rome, it had still not been observed in the human hair follicle. That is now the case, thanks to the "Hair Care, Quality and Color" team led by Bruno Bernard, working in conjunction with the aforementioned research workers in Rome.
As Sébastien Thibaut, the article's first author, explains: "The primary goal of our project was to establish a parallel between epidermal differentiation and the hair follicle's differentiation programs". These researchers have shown that of the TG family, TG2 is ubiquitous (it is found everywhere), TG1 and TG5, specific to the stratum granulosum, are found in the inner root sheath of the hair follicle, and TG3, specific to the stratum corneum, is expressed exclusively in the hair shaft.
The authors have focused discussion primarily on the complementary relationship between the TGs in the hair follicle and on TG5, which plays a key role in the physiological balance of the skin and hair. According to Sébastien Thibaut: "TG3 is also a very interesting case. This enzyme, whose use we have patented, is expressed specifically in the hair shaft. It is a key enzyme in the building and keratinization of the shaft. By influencing its activity, we can imagine numerous possible applications, perhaps - why not? - a modulation of the rigidity of the hair shaft".
Sébastien Thibaut*, Eleonora Candi, Valentina Pietroni, Gerry Melino, Rainer Schmidt* and Bruno A. Bernard*. Transglutaminase 5 Expression in Human Hair Follicle. The Journal of Investigative Dermatology 125 (3), 581-585.