scholarly journals Secreted Frizzled-related protein 4 inhibits the regeneration of hair follicles

PeerJ ◽  
2019 ◽  
Vol 6 ◽  
pp. e6153 ◽  
Author(s):  
Haiying Guo ◽  
Yizhan Xing ◽  
Fang Deng ◽  
Ke Yang ◽  
Yuhong Li
Keyword(s):  
Hair Follicle ◽  
Hair Follicles ◽  
Hair Cycle ◽  
Related Protein ◽  
Outer Root Sheath ◽  
Root Sheath ◽  
Potential Therapeutic Application ◽  
Hematoxylin And Eosin ◽  
Hair Follicle Growth ◽  
Treated Hair

Secreted Frizzled-related Protein 4 (sFRP4) belongs to Wnt inhibitors. Previously, we reported that sFRP4 inhibited the differentiation of melanocyte. Here, by using of immunostaining, we showed that sFRP4 is expressed in both human and mouse hair follicles, especially in the outer root sheath and inner root sheath. To reveal the role of sFRP4 in hair follicle growth and hair cycle, we induced synchronized hair cycle in the dorsal skin of mice by depilation, and injected sFRP4 intradermally into the skin. By hematoxylin and eosin staining, we found that the regeneration of hair follicles was inhibited by sFRP4. However, the structure of hair follicles remained complete. Compared with phosphate buffer saline-treated hair follicles, the sFRP4-treated hair follicles still had the same expression pattern of keratins. Our findings reveal that sFRP4 inhibits but not blocks the regeneration of hair follicles, and supply a potential therapeutic application to treat hair follicle regeneration disorders.

A Selectable Biomarker in Hair Follicle Cycles – Cathepsins: A Preliminary Study in Murine

2021 ◽  
pp. 1-7
Author(s):  
Jingzhu Bai ◽  
Zijian Gong ◽  
Qingfang Xu ◽  
Haiyan Chen ◽  
Qiaoping Chen ◽  
...  
Keyword(s):  
Hair Follicle ◽  
Hair Cycle ◽  
Biological Factors ◽  
Outer Root Sheath ◽  
Physiological Processes ◽  
Intervention Measures ◽  
Root Sheath ◽  
Inner Root Sheath ◽  
Preliminary Study ◽  
Paraffin Method

<b><i>Background/Objective:</i></b> Hair cycle is regulated by many biological factors. Cathepsins are involved in various physiological processes in human skin. Here, we investigated the cathepsin expression and distribution changes in follicular growth cycles for better understanding the hair cycles and to explore new intervention measures. <b><i>Methods:</i></b> The 24 mice (C57BL/6, female, 7-week old) were selected and removed the back hair via rosin/paraffin method. At Day 8, Day 20, and Day 25, biopsy on post-plucking area was done. Immunohistochemical staining, Western blot, and Q-PCR were used to test the cathepsin B/D/L/E. <b><i>Results:</i></b> In anagen, cathepsins (B, D, L, and E) were distributed in the hair follicle matrix, inner hair root sheath, and hair. In catagen, cathepsins were mainly observed in un-apoptosis inner root sheath and outer root sheath. Expression of cathepsins B-mRNA and L-mRNA was decreased from anagen and catagen to telogen. Cathepsin D-mRNA was increased in catagen and then decreased in telogen. Cathepsin E-mRNA was decreased in catagen and slightly increased in telogen. <b><i>Conclusions:</i></b> The distribution and expression of cathepsins B, D, L, and E in hair follicle changed with hair growth process which indicated that cathepsins might act as selectable biomarkers of hair cycle in different stages.

scholarly journals Inhibition of Rab27a and Rab27b Has Opposite Effects on the Regulation of Hair Cycle and Hair Growth

2020 ◽  
Vol 21 (16) ◽  
pp. 5672
Author(s):  
Kyung-Eun Ku ◽  
Nahyun Choi ◽  
Jong-Hyuk Sung
Keyword(s):  
Hair Growth ◽  
Expression Patterns ◽  
Dermal Papilla ◽  
Hair Follicles ◽  
Hair Cycle ◽  
Outer Root Sheath ◽  
Dermal Papilla Cells ◽  
Root Sheath ◽  
Culture Models

Rab27a/b are known to play an important role in the transport of melanosomes, with their knockout causing silvery gray hair. However, the relationship between Rab27a/b and hair growth is not well known. To evaluate the role of Rab27a/b in hair cycle, we investigated the expression of Rab27a/b during hair cycling and human outer root sheath (hORS) cells. The expression of Rab27a in ORS cells was mainly detected at the anagen, whereas expression of Rab27b in ORS, and epidermal cells was strongly expressed at the telogen. Additionally, Rab27a/b were expressed in the Golgi of hORS cells. To evaluate the role of Rab27a/b in hair growth, telogen-to-anagen transition animal and vibrissae hair follicles (HFs) organ culture models were assayed using Rab27a/b siRNAs. The knockdown of Rab27a or Rab27b suppressed or promoted hair growth, respectively. These results were also confirmed in human dermal papilla cells (hDPCs) and hORS cells, showing the opposite mitogenic effects. Moreover, Rab27b knockdown increased the expression levels of various growth factors in the hDPCs and hORS cells. Overall, the opposite temporal expression patterns during hair cycling and roles for hair growth of Rab27a/b suggested that Rab27a/b might regulate the hair cycle. Therefore, our study may provide a novel solution for the development of hair loss treatment by regulating Rab27a/b levels.

scholarly journals Integrin-linked kinase is required for epidermal and hair follicle morphogenesis

2007 ◽  
Vol 177 (3) ◽  
pp. 501-513 ◽  
Author(s):  
Katrin Lorenz ◽  
Carsten Grashoff ◽  
Robert Torka ◽  
Takao Sakai ◽  
Lutz Langbein ◽  
...  
Keyword(s):  
Hair Follicle ◽  
Leading Edge ◽  
Hair Shaft ◽  
Hair Follicles ◽  
Membrane Dynamics ◽  
Epidermal Keratinocytes ◽  
Outer Root Sheath ◽  
Root Sheath ◽  
Integrin Linked Kinase

Integrin-linked kinase (ILK) links integrins to the actin cytoskeleton and is believed to phosphorylate several target proteins. We report that a keratinocyte-restricted deletion of the ILK gene leads to epidermal defects and hair loss. ILK-deficient epidermal keratinocytes exhibited a pronounced integrin-mediated adhesion defect leading to epidermal detachment and blister formation, disruption of the epidermal–dermal basement membrane, and the translocation of proliferating, integrin-expressing keratinocytes to suprabasal epidermal cell layers. The mutant hair follicles were capable of producing hair shaft and inner root sheath cells and contained stem cells and generated proliferating progenitor cells, which were impaired in their downward migration and hence accumulated in the outer root sheath and failed to replenish the hair matrix. In vitro studies with primary ILK-deficient keratinocytes attributed the migration defect to a reduced migration velocity and an impaired stabilization of the leading-edge lamellipodia, which compromised directional and persistent migration. We conclude that ILK plays important roles for epidermis and hair follicle morphogenesis by modulating integrin-mediated adhesion, actin reorganization, and plasma membrane dynamics in keratinocytes.

scholarly journals Autologous, Non-Invasively Available Mesenchymal Stem Cells from the Outer Root Sheath of Hair Follicle Are Obtainable by Migration from Plucked Hair Follicles and Expandable in Scalable Amounts

Cells ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 2069
Author(s):  
Hanluo Li ◽  
Federica Francesca Masieri ◽  
Marie Schneider ◽  
Tina Kottek ◽  
Sebastian Hahnel ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Hair Follicle ◽  
Unmet Need ◽  
Hair Follicles ◽  
Outer Root Sheath ◽  
Differentiation Capacity ◽  
Prior Art ◽  
Root Sheath ◽  
Autologous Mesenchymal Stem Cells

Background: Regenerative therapies based on autologous mesenchymal stem cells (MSC) as well as stem cells in general are still facing an unmet need for non-invasive sampling, availability, and scalability. The only known adult source of autologous MSCs permanently available with no pain, discomfort, or infection risk is the outer root sheath of the hair follicle (ORS). Methods: This study presents a non-invasively-based method for isolating and expanding MSCs from the ORS (MSCORS) by means of cell migration and expansion in air–liquid culture. Results: The method yielded 5 million cells of pure MSCORS cultured in 35 days, thereby superseding prior art methods of culturing MSCs from hair follicles. MSCORS features corresponded to the International Society for Cell Therapy characterization panel for MSCs: adherence to plastic, proliferation, colony forming, expression of MSC-markers, and adipo-, osteo-, and chondro-differentiation capacity. Additionally, MSCORS displayed facilitated random-oriented migration and high proliferation, pronounced marker expression, extended endothelial and smooth muscle differentiation capacity, as well as a paracrine immunomodulatory effect on monocytes. MSCORS matched or even exceeded control adipose-derived MSCs in most of the assessed qualities. Conclusions: MSCORS qualify for a variety of autologous regenerative treatments of chronic disorders and prophylactic cryopreservation for purposes of acute treatments in personalized medicine.

scholarly journals CCN2 modulates hair follicle cycling in mice

2013 ◽  
Vol 24 (24) ◽  
pp. 3939-3944 ◽  
Author(s):  
Shangxi Liu ◽  
Andrew Leask
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Hair Follicle ◽  
Cell Activity ◽  
Adult Life ◽  
Tissue Growth ◽  
Hair Follicles ◽  
Outer Root Sheath ◽  
Root Sheath ◽  
Dermal Papillae

It is critical to understand how stem cell activity is regulated during regeneration. Hair follicles constitute an important model for organ regeneration because, throughout adult life, they undergo cyclical regeneration. Hair follicle stem cells—epithelial cells located in the follicle bulge—are activated by periodic β-catenin activity, which is regulated not only by epithelial-derived Wnt, but also, through as-yet-undefined mechanisms, the surrounding dermal microenvironment. The matricellular protein connective tissue growth factor (CCN2) is secreted into the microenvironment and acts as a multifunctional signaling modifier. In adult skin, CCN2 is largely absent but is unexpectedly restricted to the dermal papillae and outer root sheath. Deletion of CCN2 in dermal papillae and the outer root sheath results in a shortened telogen-phase length and elevated number of hair follicles. Recombinant CCN2 causes decreased β-catenin stability in keratinocytes. In vivo, loss of CCN2 results in elevated numbers of K15-positive epidermal stem cells that possess elevated β-catenin levels and β-catenin–dependent reporter gene expression. These results indicate that CCN2 expression by dermal papillae cells is a physiologically relevant suppressor of hair follicle formation by destabilization of β-catenin and suggest that CCN2 normally acts to maintain stem cell quiescence.

scholarly journals Migration of Melanoblasts into the Developing Murine Hair Follicle Is Accompanied by Transient c-Kit Expression

2002 ◽  
Vol 50 (6) ◽  
pp. 751-766 ◽  
Author(s):  
Eva M. J. Peters ◽  
Desmond J. Tobin ◽  
Natasha Botchkareva ◽  
Marcus Maurer ◽  
Ralf Paus
Keyword(s):  
Stem Cell ◽  
Hair Follicle ◽  
Stem Cell Factor ◽  
Mouse Skin ◽  
Dermal Papilla ◽  
Hair Follicles ◽  
Cell Populations ◽  
Outer Root Sheath ◽  
Hair Bulb ◽  
Root Sheath

Disruption of the c-Kit/stem cell factor (SCF) signaling pathway interferes with the survival, migration, and differentiation of melanocytes during generation of the hair follicle pigmentary unit. We examined c-Kit, SCF, and S100 (a marker for precursor melanocytic cells) expression, as well as melanoblast/melanocyte ultrastructure, in perinatal C57BL/6 mouse skin. Before the onset of hair bulb melanogenesis (i.e., stages 0–4 of hair follicle morphogenesis), strong c-Kit immunoreactivity (IR) was seen in selected non-mela-nogenic cells in the developing hair placode and hair plug. Many of these cells were S100-IR and were ultrastructurally identified as melanoblasts with migratory appearance. During the subsequent stages (5 and 6), increasingly dendritic c-Kit-IR cells successively invaded the hair bulb, while S100-IR gradually disappeared from these cells. Towards the completion of hair follicle morphogenesis (stages 7 and 8), several distinct follicular melanocytic cell populations could be defined and consisted broadly of (a) undifferentiated, non-pigmented c-Kit-negative melanoblasts in the outer root sheath and bulge and (b) highly differentiated melanocytes adjacent to the hair follicle dermal papilla above Auber's line. Widespread epithelial SCF-IR was seen throughout hair follicle morphogenesis. These findings suggest that melanoblasts express c-Kit as a prerequisite for migration into the SCF-supplying hair follicle epithelium. In addition, differentiated c-Kit-IR melanocytes target the bulb, while non-c-Kit-IR melanoblasts invade the outer root sheath and bulge in fully developed hair follicles.

scholarly journals Culturing of Melanocytes from the Equine Hair Follicle Outer Root Sheath

Processes ◽  
2021 ◽  
Vol 9 (1) ◽  
pp. 177
Author(s):  
Hanluo Li ◽  
Jule Kristin Michler ◽  
Alexander Bartella ◽  
Anna Katharina Sander ◽  
Sebastian Gaus ◽  
...  
Keyword(s):  
Hair Follicle ◽  
Hair Follicles ◽  
Outer Root Sheath ◽  
Root Sheath ◽  
Human Melanocytes ◽  
Experimental Base ◽  
Typical Morphology ◽  
Insight Into ◽  
Study Offer

Hair follicles harbor a heterogeneous regenerative cell pool and represent a putative low-to-non-invasively available source of stem cells. We previously reported a technology for culturing human melanocytes from the hair follicle outer root sheath (ORS) for autologous pigmentation of tissue engineered skin equivalents. This study translated the ORS technology to horses. We de-veloped a culture of equine melanocytes from the ORS (eMORS) from equine forelock hair follicles cultured by means of an analogue human hair follicle-based in vitro methodology. The procedure was adjusted to equine physiology by addition of equine serum to the culture medium. The hair follicles were isolated by macerating forelock skin rests, enzymatically digested and subjected to air-medium-interface cultivation method. The procedure resulted in differentiated equine melanocytes, which exhibited typical morphology, presence of melanosomes, expression of cytoskeleton proteins vimentin, α-SMA, Sox2, S100ß and tyrosinase as well as tyrosinase activity followed by production of melanin. According to all assessed parameters, eMORS could be ranked as partially melanotic melanocytes. The results of the study offer an experimental base for further insight into hair follicle biology in equine and for comparative studies of hair follicles across different species.

scholarly journals Splenic melanosis during normal murine C57BL/6 hair cycle and after chemotherapy.

2013 ◽  
Vol 60 (3) ◽  
Author(s):  
Dominika Michalczyk-Wetula ◽  
Aleksander Salwiński ◽  
Małgorzata Popik ◽  
Monika Jakubowska ◽  
Przemysław M Płonka
Keyword(s):  
Body Weight ◽  
Side Effects ◽  
Hair Follicle ◽  
Cancer Chemotherapy ◽  
Hair Loss ◽  
Murine Model ◽  
Hair Follicles ◽  
Hair Cycle ◽  
Normal Hair ◽  
Hematoxylin And Eosin

Cancer chemotherapy is associated with serious side effects, including temporary hair loss and impairment of pigmentation. We suspect that ectopic melanin deposition occurring due to chemotherapy may add to these effects worsening the already unpleasant symptoms. We associated the ectopic occurrence of follicular melanin after chemotherapy with splenic melanosis - an interesting example of extradermal melanin localization - and we expected an increase in splenic melanin deposition after chemotherapy. Using the C57BL/6 murine model of synchronized hair cycle induced by depilation, we visualized splenic melanin by means of several histological and histochemical protocols of staining: hematoxylin and eosin, May-Grünwald-Giemsa and Fontana-Masson. Unexpectedly, the splenic deposition of melanin decreased due to application of cyclophosphamide (i.p. 120 mg/ kg body weight on day 9 post depilation). The drop was abrupt and lasted for at least 5 days (day 13-18 post depilation), as compared with normal hair cycle. Moreover, in mice with normal, depilation-induced hair cycle we observed a similar drop shortly before entering catagen (day 15 post depilation), followed by a slow and partial increase in splenic melanization up to day 27 post depilation in both groups. We conclude that cyclophosphamide negatively affects splenic melanization and/or extradermal transfer of ectopic melanin from the dystrophic hair follicles, but the most powerful down-regulator of splenic melanosis is normal and dystrophic catagen - the phase of hair follicle involution and re-modelling.

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