Oleanolic acid (OA) is a pentacyclic triterpenoid with favourable physiological activity. It is widely distributed in more than 200 species of plants. OA has garnered significant interest because of its potential biological activities, such as antioxidant, bacteriostatic, and hair growth-promoting effects. To study the effect of OA on hair growth and related mechanisms, we investigated hair growth in mice with testosterone-induced androgenetic alopecia (AGA) that were treated with three different concentrations of OA. The antioxidant, bacteriostatic, and cytotoxic effects of OA were evaluated. We found that mice with testosterone-induced AGA treated with 1% or 0.5% OA showed significantly enhanced hair growth and increased vascular endothelial growth factor/glyceraldehyde-3-phosphate dehydrogenase ratio and levels of fibroblast growth factor receptor and insulin-like growth factor 1. Using an immunofluorescence staining assay, we demonstrated that β-catenin, a key Wnt signalling transducer, was highly expressed in the OA-treated groups. These results suggest that OA may promote hair growth by stimulating hair matrix cell proliferation via the Wnt/β-catenin pathway and lowering the levels of tumour necrosis factor-alpha, and transforming growth factor-beta 1, dihydrotestosterone, and 5α-reductase.
- MeSH
- alopecie chemicky indukované farmakoterapie metabolismus MeSH
- antioxidancia MeSH
- beta-katenin * metabolismus MeSH
- cytokiny MeSH
- kyselina olenalová * farmakologie MeSH
- myši MeSH
- testosteron MeSH
- vaskulární endoteliální růstový faktor A metabolismus MeSH
- vlasový folikul metabolismus patologie MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
In accordance with the 3 Rs principle (to replace, reduce and refine) animal models in biomedical research, we have developed and applied a new approach for sampling and analyzing hair follicles in various experimental settings. This involves use of a convenient device for non-invasive collection of hair follicles and processing methods that provide sufficient amounts of biological material to replace stressful and painful biopsies. Moreover, the main components of hair follicles are live cells of epithelial origin, which are highly relevant for most types of malignant tumors, so they provide opportunities for studying aging-related pathologies including cancer. Here, we report the successful use of the method to obtain mouse hair follicular cells for genotyping, quantitative PCR, and quantitative immunofluorescence. We present proof of concept data demonstrating its utility for routine genotyping and monitoring changes in quality and expression levels of selected proteins in mice after gamma irradiation and during natural or experimentally induced aging. We also performed pilot translation of animal experiments to human hair follicles irradiated ex vivo. Our results highlight the value of hair follicles as biological material for convenient in vivo sampling and processing in both translational research and routine applications, with a broad range of ethical and logistic advantages over currently used biopsy-based approaches.
- MeSH
- fluorescenční protilátková technika MeSH
- genotypizační techniky MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- ocas patologie MeSH
- poškození DNA * účinky záření MeSH
- stárnutí patologie fyziologie MeSH
- vlasový folikul anatomie a histologie metabolismus fyziologie účinky záření MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The skin surface is modified by numerous appendages. These structures arise from epithelial stem cells (SCs) through the induction of epidermal placodes as a result of local signalling interplay with mesenchymal cells based on the Wnt-(Dkk4)-Eda-Shh cascade. Slight modifications of the cascade, with the participation of antagonistic signalling, decide whether multipotent epidermal SCs develop in interfollicular epidermis, scales, hair/feather follicles, nails or skin glands. This review describes the roles of epidermal SCs in the development of skin adnexa and interfollicular epidermis, as well as their maintenance. Each skin structure arises from distinct pools of epidermal SCs that are harboured in specific but different niches that control SC behaviour. Such relationships explain differences in marker and gene expression patterns between particular SC subsets. The activity of well-compartmentalized epidermal SCs is orchestrated with that of other skin cells not only along the hair cycle but also in the course of skin regeneration following injury. This review highlights several membrane markers, cytoplasmic proteins and transcription factors associated with epidermal SCs.
- MeSH
- buněčná diferenciace genetika MeSH
- epidermální buňky metabolismus patologie MeSH
- epidermis metabolismus patologie MeSH
- kmenové buňky metabolismus patologie MeSH
- kůže patologie MeSH
- lidé MeSH
- signální transdukce genetika MeSH
- vlasový folikul metabolismus patologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Hair follicles are unique organs undergoing regular cycles of proliferation, differentiation, and apoptosis. The final step of apoptosis is, in general, mediated by executioner caspases comprising caspase-3, -6 and -7. Despite their commonly accepted apoptotic function, executioner caspases also participate in non-apoptotic processes. In the present study, we investigated activation (cleavage) of caspase-7 in mouse hair follicles and surrounding tissue during embryonic development into adulthood. Casp7 (-/-) mice were examined to understand the effect of caspase-7 deficiency in the skin. The activated form of caspase-7 was observed during embryonic hair follicle development, as well as in the first hair cycle. In general, activation of caspase-7 did not correlate with apoptosis and activation of caspase-3, except during physiological hair follicle regression. Notably, cleaved caspase-7 was observed in mast cells and its deficiency in the adult skin resulted in increased mast cell number. Our study shows for the first time activated caspase-7 in hair follicles and mast cells and indicates its non-apoptotic roles in the skin.
- MeSH
- aktivace enzymů MeSH
- apoptóza * MeSH
- exprese genu MeSH
- kaspasa 3 metabolismus MeSH
- kaspasa 7 nedostatek genetika metabolismus MeSH
- kaspasy genetika metabolismus MeSH
- kůže embryologie metabolismus MeSH
- mastocyty metabolismus MeSH
- myši knockoutované MeSH
- myši MeSH
- počet buněk MeSH
- transport proteinů MeSH
- vlasový folikul embryologie metabolismus MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Apoptosis in hair follicles often is studied under pathological conditions; little is known about apoptotic mechanisms during normal hair follicle formation and maintenance. We investigated proteins of intrinsic apoptotic pathway, Bim and Puma, during hair follicle development and the first catagen stage using immunofluorescence to describe their expression patterns and to correlate them with apoptosis as determined by TUNEL assay. Both proteins were found in developing follicles. Bim and Puma overlapped apoptosis only partially during physiological apoptotic stage and they were present in non-apoptotic parts of the follicles. Our findings suggest that these primary apoptotic molecules participate in postnatal development and maintenance of hair follicles.
- MeSH
- apoptóza fyziologie MeSH
- barvení a značení metody MeSH
- fluorescenční protilátková technika metody MeSH
- koncové značení zlomů DNA in situ metody MeSH
- membránové proteiny metabolismus MeSH
- myši MeSH
- nádorové supresorové proteiny metabolismus MeSH
- proteiny regulující apoptózu metabolismus MeSH
- protoonkogenní proteiny metabolismus MeSH
- vlasový folikul cytologie metabolismus MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Hair follicles undergo repetitive stages of cell proliferation and programmed cell death. The catagen stage of physiological apoptosis is connected with dynamic changes in morphology and alterations in gene expression. However, hair follicle apoptosis must be in balance with events in surrounding tissues, such as keratinocyte cornification, to maintain complex skin homeostasis. Several pro- and anti-apoptotic molecules in the skin have been reported but mainly in pathological states. In this investigation, apoptosis-related gene expression was examined during the first catagen stage of mouse hair follicle development by PCR arrays under physiological conditions. Postnatal stages P15 and P17, representing early and late catagen stages, were evaluated relatively to stage P6, representing the hair follicle growing phase, to demonstrate dynamics of gene activation during the catagen. Several statistically significant alterations were observed at P15 and particularly at P17. Bnip3L and caspase-12 identified by the PCR arrays at both catagen stages were additionally localized using immunofluorescence and were reported in physiological hair development for the first time.
- MeSH
- apoptóza fyziologie MeSH
- kaspasa 12 biosyntéza MeSH
- kůže cytologie metabolismus MeSH
- membránové proteiny biosyntéza MeSH
- mitochondriální proteiny biosyntéza MeSH
- myši MeSH
- regulace genové exprese fyziologie MeSH
- vlasový folikul cytologie metabolismus MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Hair follicle morphogenesis depends on Wnt, Shh, Notch, BMP and other signaling pathways interplay between epithelial and mesenchymal cells. The Wnt pathway plays an essential role during hair follicle induction, Shh is involved in morphogenesis and late stage differentiation, Notch signaling determines stem cell fate while BMP is involved in cellular differentiation. The Wnt pathway is considered to be the master regulator during hair follicle morphogenesis. Wnt signaling proceeds through EDA/EDAR/NF-κB signaling. NF-κB regulates the Wnt pathway and acts as a signal mediator by upregulating the expression of Shh ligand. Signal crosstalk between epithelial and mesenchymal cells takes place mainly through primary cilia. Primary cilia formation is initiated with epithelial laminin-511 interaction with dermal β-1 integrin, which also upregulates expression of downstream effectors of Shh pathway in dermal lineage. PDGF signal transduction essential for crosstalk is mediated through epithelial PDGF-A and PDGFRα expressed on the primary cilia. Dermal Shh and PDGF signaling up-regulates dermal noggin expression; noggin is a potent inhibitor of BMP signaling which helps in counteracting BMP mediated β-catenin inhibition. This interplay of signaling between the epithelial and dermal lineage helps in epithelial Shh signal amplification. The dermal Wnt pathway helps in upregulation of epithelial Notch expression. Dysregulation of these pathways leads to certain abnormalities and in some cases even tumor outgrowth.
- MeSH
- lidé MeSH
- morfogeneze * MeSH
- nemoci vlasů genetika metabolismus MeSH
- signální transdukce * MeSH
- vlasový folikul růst a vývoj metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
The Myb transcription factors are involved in essential cellular processes, such as cell proliferation, differentiation and cell death. Biological functions carried out by specific Myb proteins are distinct. Hair follicles are ectodermal-derived organs with cycling character of the growth resulting from the presence of somatic stem cells. In this study, we followed the expression of the Myb proteins in developing hair follicles and in the hair follicle stem cell niche by immunofluorescence staining. During hair follicle development, B-Myb was present in a few cells located in the area of cell division; c-Myb was abundant postanally in dividing cells but also in keratinizing zone. In addition, c-Myb was also detected in cells under the hair follicle bulge. These findings indicate possible involvement of c-Myb in regulation of activated stem cells leaving the niche.
β -catenin signaling is required for hair follicle deve lopment and regeneration which are involved in the resuscitation of hair follicle stem cells (HFSCs). To further characterize the role of β -catenin in the regulation of proliferation of HFSCs, the β -catenin expression was measured in the defined stages of hair follicle cycle and the proliferative potency was determined by using an in vitro cell growth assay. Our results showed that activation of β -catenin correlated with HFSCs proliferation, which appeared to be mediated by the nuclear translocation of stabilized β -catenin and the activation of responsib le cell cycle genes (cyclin D1 and p21). In addition, PI3K/Akt pathway was also involved in the HFSCs proliferation, partly regulated by β -catenin signaling pathway. These results demonstrate that β -catenin is an essential factor in the regulation of HFSCs proliferation via PI3K/Akt pathway and might be a potential therapeutic target for the regulation of the yield of keratinocytes from HFSCs.
- Klíčová slova
- PI3K/Akt,
- MeSH
- beta-katenin * MeSH
- cyklin D1 MeSH
- fosfatidylinositol-3-kinasy MeSH
- imunohistochemie MeSH
- jaderné proteiny MeSH
- kmenové buňky * MeSH
- krysa rodu rattus MeSH
- onkogenní protein p21(ras) MeSH
- proliferace buněk MeSH
- transkripční faktory MeSH
- vlasový folikul * metabolismus růst a vývoj MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
- Publikační typ
- práce podpořená grantem MeSH
The authors report an unusual case of intrafollicular collagenous crystalloids in an 86-year-old woman. The presence of collagenous crystalloids within the follicular epithelium is intriguing and has not been described previously.
- MeSH
- diferenciální diagnóza MeSH
- isotonické roztoky analýza MeSH
- kolagen analýza metabolismus MeSH
- krystalizace MeSH
- lidé MeSH
- nádory kůže diagnóza MeSH
- nemoci vlasů metabolismus patologie MeSH
- nos MeSH
- senioři nad 80 let MeSH
- spinocelulární karcinom diagnóza MeSH
- vlasový folikul chemie metabolismus patologie MeSH
- Check Tag
- lidé MeSH
- senioři nad 80 let MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
