Jean Francois Michelet

The anti-ageing potential of a new jasmonic acid derivative (LR2412): in vitro evaluation using reconstructed epidermis episkin™

Abstract:  Jasmonic acid is involved in plant wound repair and tissue regeneration, but no study has been reported in human skin. The effect of a jasmonic acid derivative, tetra‐hydro‐jasmonic acid (LR2412, 1 and 10 μm) was investigated on an in vitro reconstructed skin model, Episkin™. Using real time RTQPCR studies, results showed an increase in hyaluronan synthase 2 (HAS2) and hyaluronase synthase 3 (HAS3) expression. Furthermore, an increase in hyaluronic acid (HA) deposits in basal and suprabasal layers of the epidermis was observed. The percentage of positive Ki67 keratinocytes in the basal layer as well as the epidermis thickness were seen to increase. Immunohistochemistry studies showed that the synthesis of late differentiation proteins filaggrin and transglutaminase 1 was not modified. The human epidermis is known to thin with age while HA content has been reported to decrease. These results illustrate the potential of LR2412 in counteracting signs of skin ageing.

Human Hair Follicle Stem/Progenitor Cells Express Hypoxia Markers

TO THE EDITOR Hair is produced by a specialized skin appendage comprising the pilosebaceous unit and associated structures. Hair growth, tightly regulated by growth factors, cytokines, neuropeptides, hormones, and environmental cues, is not a continual process and cyclical hair follicle renewal requires activation of local reservoirs of stem cells. Seminal work in mice localized a reservoir of slow cycling, epithelial stem cells in the bulge, a distinct segment of the outer root sheath (ORS) of mouse follicles (Cotsarelis et al., 1990). It is now known that the follicle is endowed with numerous stem cell reservoirs, including a Lgr5þ , actively cycling cell population in the lower ORS (Jaks et al., 2008), and that these reservoirs express different markers and seem to have different functions (Jaks et al., 2010). With respect to human hair follicles, early work suggested the existence of at least two pools of pluripotent cells (Lenoir et al., 1988). In accordance with these findings, high b1-integrin (CD29) expression, which has been associated with epithelial stem cells (Jones and Watt, 1993), is observed in sections of both the upper and lower ORS (Commo and Bernard, 1997). In addition, keratin 19 (K19) labeling clearly identifies two groups of putative stem cells in the hair follicle. Although upper ORS K19þ cells are negative for the proliferation marker Ki67, some lower ORS K19þ cells are Ki67þ suggesting that, as in mouse follicles, both quiescent and active stem cells are present in human hair follicles (Commo et al., 2000). The upper and lower reservoirs of K19þ cells are not, however, identical and can be distinguished by differential expression of K15 and CD200, more highly expressed in the upper reservoir, and CD271, CD29, and CD34, more highly expressed in the lower reservoir (Inoue et al., 2009). This differential epitope mapping appears to not be restricted to the ORS as the connective tissue sheath (CTS) in conjunction with these two reservoirs also harbors distinct compartments. For example, one chondroitin sulfate epitope (4C3-CS) is specific for the upper CTS while another chondroitin sulfate epitope (7D4-CS) and N-sulfated D-glucuronic acid-rich heparin sulfate (HepSS-1 epitope) are only observed in the lower CTS (Malgouries et al., 2008). In summary, the human hair follicle can be characterized by the presence of at least two epithelial stem cell reservoirs that interact with specific microenvironments. Considering the essential role of the niche in stem cell maintenance and function, we are interested in microenvironmental factors that influence human hair follicle stem cells. The human hair follicle is considered as Accepted article preview online 8 March 2013; published online 11 April 2013 Abbreviations: CA IX, carbonic anhydrase IX; CTS, connective tissue sheath; GLUT1, glucose transporter 1; HIF1, hypoxia-inducible transcription factor 1; K19, keratin 19; ORS, outer root sheath M Rathman-Josserand et al. Human Hair Follicle Stem/Progenitor Cell

Expression of NAD+ dependent 15-hydroxyprostaglandin dehydrogenase and protection of prostaglandins in human hair follicle

Abstract:  NAD+ dependent 15‐hydroxyprostaglandin dehydrogenate (15‐PGDH) catalyses oxidation of 15(S)‐hydroxyl group of prostaglandins and as a result inactivates their physiological potential. Positive effects of prostaglandins or prostaglandin analogues were reported on terminal hair, vellus hair or eyelash growth and a complex prostaglandin network was recently described in human hair follicle. In the present study, we showed that 15‐PGDH was expressed in human hair follicle mainly in melanocytes and keratinocytes, which brought us to consider this enzyme as a possible target to sustain local prostaglandin production. Using a recombinant enzymatic strategy, specific 15‐PGDH inhibitors were screened. We identified a thiazolidine dione derivative exhibiting efficacy on follicular outer root sheath keratinocytes, since it concomitantly decreased the production of deactivated 13,14 dihydro 15‐ketoprostaglandin F2α and sustained prostaglandin F2αin vitro production. In the context of recent interest in prostaglandins and prostaglandin analogues as hair regrowth agents, we postulated that the use of selected 15‐PGDH inhibitors could reinforce or prolong the effect of these physiological mediators on hair and skin.