|Year : 2011 | Volume
| Issue : 3 | Page : 17-19
Session H: Mechanism, Diagnosis and Treatment of Hair Disorders
|Date of Web Publication||16-Jun-2011|
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
. Session H: Mechanism, Diagnosis and Treatment of Hair Disorders. Int J Trichol 2011;3, Suppl S1:17-9
The enhancement of hair growth by valproic acid is mediated through GSK-3β inhibition
Seong Jin Jo*, Soon Jin Choi, Sun Young Yoon, Kwang Hyun Cho, Kyu Han Kim, Hee Chul Eun, Oh Sang Kwon
Department of Dermatology, Seoul National University College of Medicine, Seoul, Korea.
Human hair follicles are self-renewing structures, which undergo three phase of hair cycle; anagen, catagen, and telogen. β-catenin, the transducer of Wnt signaling, is critical in development and growth of hair. In the absence of Wnt signals, cytoplasmic β-catenin is maintained at low level through regulation by GSK-3, multifunctional serine/threonin kinase. After phosphorylation by GSK-3, β-catenin is ubiquitinated and degraded in cytoplasm. Therefore, inhibition of GSK-3 is able to increase β-catenin in nucleus and would be able to induce growth of hair. Valproic acid (VPA) is an anticonvulsant and mood-stabilizing drug used for decades and is known to inhibit the GSK-3β. In our study, VPA enhanced the proliferation of human dermal papilla cells (DPCs) and outer root sheath (ORS) cells. When DPCs were treated with VPA, β-catenin was shown to be accumulated in the nucleus of DPCs by immunocytochemistry. Using human hair follicle organ culture, we found that hair follicles treated with VPA showed more rapid elongation of hair. Topical application of VPA on the back of 7 week old female C57BL/6 mice accelerated hair growth compared to control. In conclusion, we think that VPA can enhance hair growth through inhibition of GSK-3β and would become a potential alternative for treatment of alopecia.
The roles of the Hippo pathway effector YAP in hair follicle development
Uri Gat*, Neta Haim, Eli Raveh
Department of Cell and Developmental Biology, The Alexander Silberman Institute of Life Sciences, The Hebrew University, Jerusalem, Israel.
In the past decade a new developmental pathway has been discovered, which was termed The YAP/hippo pathway. This signaling cascade plays an important role in animal organ size control, which it exerts by regulating tissue proliferation and apoptosis rates as a response to developmental cues, cell contact and density. Mutations in YAP and other members of this pathway were also shown to be involved in tumor formation and in various cancers. The major effector of this pathway is a transcriptional coactivator named yes-associated protein (YAP), which together with TEAD DNA binding factors and other nuclear proteins activates the pathway's targets. In this work we have produced inducible transgenic mice, which strongly and specifically express a YAP construct in the skin and hair follicles. This expression led to a striking phenotype of over-proliferation of epidermis and change in the hair morphology and growth pattern, which led to loss of most of the hair in the mutant mice. As we can control the onset of expression and also turn it off in these inducible transgenic mice, we gained insight about the effect of this pathway in different stages of skin and hair development. Current work is in progress to identify the molecular base for the function of this important and little explored pathway in skin and in particular in the hair follicles.
Steroid synthesis by human hair follicle; implications for hair diseases
Elena Pomari 1,3 *, Marco Massironi 2 , Luisa Dalla Valle 1 , Lorenzo Colombo 1 , M. Julie Thornton 3
1 Comparative Endocrinology Laboratory, Department of Biology, University of Padova, Padova, Italy; 2 Cutech, Padova, Italy; 3 Centre for Skin Sciences, University of Bradford, Bradford, UK.
Dehydropiandrosterone sulphate (DHEA-S) an abundant circulating steroid distinguishing humans from other mammals, provides a precursor for potent steroids testosterone and estradiol. Although steroids have important modulatory effects on human hair follicles (HFs), the mechanisms by which they regulate hair growth are poorly understood. Therefore, we have analyzed mRNA expression of key steroidogenic proteins P450scc, P450c17, P450arom, steroid sulfatase, OATP2B1 and 5α-reductase 1 and 2 in female HFs (n=5 donors). The receptor expression (AR, ERα, ERß) by RT PCR was also confirmed. The whole transcriptome was analyzed by gene expression array following 24h incubation with DHEA-S (10μM), testosterone (50nM) and estradiol (1nM). HFs expressed all steroidogenic genes investigated. Gene expression array revealed large changes: estradiol (268 up-regulated, 167 down-regulated), testosterone (503 up-regulated, 245 down-regulated) DHEA-S (608 up-regulated, 230 down-regulated). Grouping analysis revealed significant modulation by estradiol of genes involved in cell proliferation, migration and differentiation, and apoptosis. These studies provide evidence for estrogen synthesis from cholesterol and circulating DHEA-S. Therefore, understanding regulation of steroid availability and their paracrine, autocrine and intracrine mechanisms in the human HF may have implications for poorly controlled hair disorders such as alopecia and hirsutism.
Methotrexate treatment of alopecia areata
Andrew McDonagh*, Andrew Messenger
Department of Dermatology, Royal Hallamshire Hospital, Sheffield, UK.
The inefficacy or excessive side-effects of therapy in alopecia areata (AA) often make treatment difficult for both doctor and patient. Low-dose oral methotrexate (MTX) is well established as a treatment for a range of inflammatory and autoimmune disorders affecting the skin and other organs and has recently been suggested in a series from France to be efficacious in over 50% of cases of AA. We have treated seven AA patients with MTX. Four were treated purely for AA, one also for rheumatoid arthritis and two for psoriasis. A patient treated primarily for psoriasis who also had a recent onset of alopecia subtotalis experienced excellent regrowth of hair and resolution of psoriasis on methotrexate 7.5mg weekly over 18 months. The regrowth was judged likely to be spontaneous on clinical grounds. The patient treated for rheumatoid arthritis which was well controlled on a combination of MTX 10mg weekly with sulphasalazine 1g bd continued to develop patchy AA often improving with intralesional steroid injections over more than 10 years of follow-up. A patient with extensive patchy AA of the scalp and marked trachyonychia experienced resolution of the nail changes but no regrowth of hair on methotrexate 20mg weekly over 6 months. The other patients showed no signs of hair regrowth on MTX despite doses of up to 25mg weekly maintained for up to six months. Although MTX has been reported beneficial, there is insufficient evidence at present to support its routine use in AA without further support from a randomised controlled trial.
The E3 ubiquitin ligase itch, a negative regulator of NF-kB and inflammation, is decreased in alopecia areata
Joaquin J. Jimenez 1 *, Lattouf Carol 1 , Tongyu Cao 1 , Noula Shembade 2 , Edward Harhaj 2
1 Department of Dermatology and Cutaneous Surgery, University of Miami, Miller School of Medicine, University of Miami, 2 Department of Microbiology and Immunology, Sylvester Comprehensive Cancer Center, Miami Florida, USA.
Alopecia Areata (AA) is one of the most common forms of alopecia, with a prevalence of 0.5-2%. The pathophysiology of AA remains to be completely elucidated, however it is believed that the innate and the adaptive immune systems are involved. AA lesions are characterized by peri- and intra-follicular infiltration of CD4+ and CD8+ lymphocytes. Anecdotal evidence indicates that statins may reduce the inflammatory events in AA. Much progress in the area of AA research has been made with the use of the C3H/HeJ mice, which spontaneously develop alopecia areata in approximately 20 percent of the animals by 18 months of age. In this regard, we have demonstrated that by inducing heat shock protein 70 (HSPA) with topical heat application, we can significantly accelerate the development of AA, while maintaining the same rate of symptomatic animals. Heat shock protein 70 is a known activator of the immune system, which explains the advancement of AA in this model. We therefore proposed to test the expression of the E3 ubiquitin ligase Itch, a negative regulator of NF-kB and inflammation. Our results indicate that Itch was significantly decreased in splenic T lymphocytes of heat shock-induced AA and spontaneous AA. Furthermore, NF-kB activation was enhanced as observed by IkBa phosphorylation in HSP-treated AA mice. These effects were abrogated upon treatment with statins. These findings lend further credence to the immune aspect of AA and provide a novel pathway in which to study its inflammatory events.
Automated digital image analysis (TrichoScan® ) - ease versus errors?
Punit Saraogi*, Rachita Dhurat
Departments of Dermatology, Venerology and Leprosy, T.N.Medical College and B.Y.L.Nair Ch. Hospital, Mumbai, India.
TrichoScan® is considered time-saving, easy-to-perform and consistent for quantifying hair-loss/growth. Conflicting results of our study lead us to closely observe the image-analysis, and repeated errors were highlighted. We wanted to assess the utility of TrichoScan in quantification of diffuse hair-loss in males with Androgenetic-alopecia and females with diffuse telogen hair-loss, with regard to total hair density (THD), telogen (T%) and vellus (V%) hair percentages. TrichoScan performed on 77 cases and 20 controls. In cases, THD decreased with increasing severity of alopecia. Surprisingly, 85% of the healthy volunteers had an unexplained abnormal T% of >20. Also, T% was not significantly different between cases and controls. Also, 65% of the patients with advanced thinning of hair didn't have expected elevation of V%. Multiple errors were highlighted in hair detection by software viz, at the exit points of follicular ostia, at places where hair strand thickness was not uniform throughout its length, where there was crossing, overlapping of the neighboring strands, and when more than one hair emerged from a single ostium. TrichoScan is promoted as a validated and precise tool for measurement of hair growth parameters. Under certain conditions, it may seem suitable for clinical trials evaluating treatment response. We provide evidence that this is an overstatement. This study concludes that TrichoScan-analyzed anagen/telogen hair detection is not optimal, there is overestimation of THD and the V% doesn't correlate with clinical severity of alopecia. The current TrichoScan, though easy-to-use, is error-prone and awaits refinement.
Effect of sebocytes cultured from nevus sebaceous on hair growth
Weon Ju Lee*, Hyun Wuk Cha, Han Jin Jung, Jae Hun Jun, Won Young Suk 1 , Young Kwan Sung 1 , Seok-Jong Lee, Do Won Kim
Department of Dermatology and 1 Immunology, Kyungpook National Unitversity School of Medicine, Daegu, Korea.
This study was conducted to investigate the influence of sebaceous glands on hair growth in nevus sebaceous. Sebocytes were cultured from sebaceous glands separated from nevus sebaceous. Microarray was used to compare gene expression between nevus sebaceous sebocytes and normal scalp hair sebocytes. Supernatants were collected at the time of 50% and 80% confluency of sebocytes. The supernatants were added to the culture dishes containing outer root sheath cells (ORSC) or dermal papilla cells (DPC) of hair follicle at ratios of 20%, 40%, 60%, 80%, and 100% in volume. Cell survival rate was measured with MTT assay. For examination with hair organ culture, seven follicular hair units obtained from normal scalp were cultured with supernatants collected at the time of 40% and 90% confluency of sebocytes. Microarray with sebocytes of nevus sebaceous resulted in an increase in expression of DKK1 and KRT15, which are associated with reduced hair growth. MTT assay for cell survival rate showed a decrease in that of ORSC and DPC in all conditions. The examination with hair organ culture exhibited decreased hair growth in supernatant-treated groups compared with an untreated control group. In conclusion, sebocytes of nevus sebaceous contain bioactive factors suppressing hair growth. The bioactive factors need to be examined for the development of efficacious air removal agents.