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 The Glypican-1/HGF/C-Met and Glypican-1/VEGF/VEGFR2 Ternary Complexes Regulate Hair Follicle Angiogenesis

2021 ◽  
Vol 9 ◽  
Author(s):  
Charlie Colin-Pierre ◽  
Nicolas Berthélémy ◽  
Nicolas Belloy ◽  
Louis Danoux ◽  
Vincent Bardey ◽  
...  
Keyword(s):  
Hair Follicle ◽  
Dermal Papilla ◽  
Human Keratinocytes ◽  
Hair Follicles ◽  
Microvascular Endothelial Cell ◽  
Outer Root Sheath ◽  
Dermal Papilla Cells ◽  
Root Sheath ◽  
Microvascular Endothelial

The hair renewal involves changes in the morphology of the hair follicle and its micro-vascularization. In alopecia, the hair cycle is accelerated, resulting in the formation of thinner and shorter hair. In addition, alopecia is associated with a decrease in the micro-vascularization of the hair follicles. In this study, the role of glypicans (GPCs) was analyzed in the regulation of the angiogenesis of human dermal microvascular endothelial cells (HDMEC). The analysis of glypican gene expression showed that GPC1 is the major glypican expressed by human keratinocytes of outer root sheath (KORS), human hair follicle dermal papilla cells (HHFDPC) and HDMEC. KORS were demonstrated to secrete VEGF and HGF. The HDMEC pseudotube formation was induced by KORS conditioned media (KORSCM). It was totally abrogated after GPC1 siRNA transfection of HDMEC. Moreover, when cleaved by phospholipase C (PLC), GPC1 promotes the proliferation of HDMEC. Finally, GPC1 was shown to interact directly with VEGFR2 or c-Met to regulate angiogenesis induced by the activation of these receptors. Altogether, these results showed that GPC1 is a key regulator of microvascular endothelial cell angiogenesis induced by VEGF and HGF secreted by KORS. Thus, GPC1 might constitute an interesting target to tackle alopecia in dermatology research.

scholarly journals miR-140-5p in Small Extracellular Vesicles From Human Papilla Cells Stimulates Hair Growth by Promoting Proliferation of Outer Root Sheath and Hair Matrix Cells

2020 ◽  
Vol 8 ◽  
Author(s):  
Yuxin Chen ◽  
Junfei Huang ◽  
Zhen Liu ◽  
Ruosi Chen ◽  
Danlan Fu ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Extracellular Vesicles ◽  
Hair Growth ◽  
Dermal Papilla ◽  
Luciferase Reporter ◽  
Outer Root Sheath ◽  
Dermal Papilla Cells ◽  
Root Sheath ◽  
Hair Matrix ◽  
Low Passage

The application of dermal papilla cells to hair follicle (HF) regeneration has attracted a great deal of attention. However, cultured dermal papilla cells (DPCs) tend to lose their capacity to induce hair growth during passage, restricting their usefulness. Accumulating evidence indicates that DPCs regulate HF growth mainly through their unique paracrine properties, raising the possibility of therapies based on extracellular vesicles (EVs). In this study, we explored the effects of EVs from high- and low-passage human scalp follicle dermal papilla cells (DP-EVs) on activation of hair growth, and investigated the underlying mechanism. DP-EVs were isolated by ultracentrifugation and cultured with human scalp follicles, hair matrix cells (MxCs), and outer root sheath cells (ORSCs), and we found low-passage DP-EVs accelerated HF elongation and cell proliferation activation. High-throughput miRNA sequencing and bioinformatics analysis identified 100 miRNAs that were differentially expressed between low- (P3) and high- (P8) passage DP-EVs. GO and KEGG pathway analysis of 1803 overlapping target genes revealed significant enrichment in the BMP/TGF-β signaling pathways. BMP2 was identified as a hub of the overlapping genes. miR-140-5p, which was highly enriched in low-passage DP-EVs, was identified as a potential regulator of BMP2. Direct repression of BMP2 by miR-140-5p was confirmed by dual-luciferase reporter assay. Moreover, overexpression and inhibition of miR-140-5p in DP-EVs suppressed and increased expression of BMP signaling components, respectively, indicating that this miRNA plays a critical role in hair growth and cell proliferation. DP-EVs transport miR-140-5p from DPCs to epithelial cells, where it downregulates BMP2. Therefore, DPC-derived vesicular miR-140-5p represents a therapeutic target for alopecia.

scholarly journals Stem cell factor/c-Kit signalling in normal and androgenetic alopecia hair follicles

2008 ◽  
Vol 197 (1) ◽  
pp. 11-23 ◽  
Author(s):  
Valerie A Randall ◽  
Tracey J Jenner ◽  
Nigel A Hibberts ◽  
Isabel O De Oliveira ◽  
Tayyebeh Vafaee
Keyword(s):  
Stem Cell ◽  
Stem Cell Factor ◽  
Hair Growth ◽  
Dermal Papilla ◽  
Hair Follicles ◽  
Androgenetic Alopecia ◽  
Hair Colour ◽  
Outer Root Sheath ◽  
Dermal Papilla Cells ◽  
Factor C

Androgens stimulate many hair follicles to alter hair colour and size via the hair growth cycle; in androgenetic alopecia tiny, pale hairs gradually replace large, pigmented ones. Since stem cell factor (SCF) is important in embryonic melanocyte migration and maintaining adult rodent pigmentation, we investigated SCF/c-Kit signalling in human hair follicles to determine whether this was altered in androgenetic alopecia. Quantitative immunohistochemistry detected three melanocyte-lineage markers and c-Kit in four focus areas: the epidermis, infundibulum, hair bulb (where pigment is formed) and mid-follicle outer root sheath (ORS). Colocalisation confirmed melanocyte c-Kit expression; cultured follicular melanocytes also exhibited c-Kit. Few ORS cells expressed differentiated melanocyte markers or c-Kit, but NKI/beteb antibody, which also recognises early melanocyte-lineage antigens, identified fourfold more cells, confirmed by colocalisation. Occasional similar bulbar cells were seen. Melanocyte distribution, concentration and c-Kit expression were unaltered in balding follicles. Androgenetic alopecia cultured dermal papilla cells secreted less SCF, measured by ELISA, than normal cells. This identifies three types of melanocyte-lineage cells in human follicles. The c-Kit expression by dendritic, pigmenting, bulbar melanocytes and rounded, differentiated, non-pigmenting ORS melanocytes implicate SCF in maintaining pigmentation and migration into regenerating hair bulbs. Less differentiated, c-Kit-independent cells in the mid-follicle ORS stem cell niche and occasionally in the bulb, presumably a local reserve for long scalp hair growth, implicate other factors in activating stem cells. Androgens appear to reduce alopecia hair colour by inhibiting dermal papilla SCF production, impeding bulbar melanocyte pigmentation. These results may facilitate new treatments for hair colour changes in hirsutism, alopecia or greying.

scholarly journals Localization of TIMP in cycling mouse hair

Development ◽  
1991 ◽  
Vol 111 (4) ◽  
pp. 877-879
Author(s):  
T.T. Kawabe ◽  
T.J. Rea ◽  
A.M. Flenniken ◽  
B.R. Williams ◽  
V.E. Groppi ◽  
...  
Keyword(s):  
Connective Tissue ◽  
Gene Activation ◽  
Dermal Papilla ◽  
Growth Cycle ◽  
Hair Follicles ◽  
Tissue Inhibitor Of Metalloproteinase ◽  
Hair Cycle ◽  
Dermal Papilla Cells ◽  
Root Sheath ◽  
Timp Gene

TIMP (tissue inhibitor of metalloproteinase) is a glycoprotein inhibitor of metalloproteinases that we hypothesize to be involved in the tissue remodeling that occurs during each hair growth cycle. We examined this hypothesis by studying the expression of TIMP at selected times during a single hair cycle using TIMP-lacZ transgenic mice to localize TIMP gene activity in the hair follicle. TIMP gene induction was visualized by staining mouse back skin for beta-galactosidase (beta-gal) activity. Paraffin sections were analyzed for the localization of TIMP expression. TIMP gene activation appears in hair follicles only during the mid-anagen (the growing stage of the hair cycle) primarily in Henle's layer of the inner root sheath. Some expression of TIMP is also seen in a few connective tissue cells, in the sebaceous gland and in cells at the proximity of the dermal papilla cells in catagen (regressing) and telogen (resting) follicles. These results are consistent with a role for TIMP in cyclic remodeling of connective tissue in hair follicles.

Hormones and Hair Growth: Variations in Androgen Receptor Content of Dermal papilla Cells Cultured from Human and Red Deer (Cervus Elaphus) Hair Follicles.

1993 ◽  
Vol 101 (s1) ◽  
pp. 114S-120S ◽  
Author(s):  
Valerie Anne Randall ◽  
Margaret Julie Thornton ◽  
Andrew Guy Messenger ◽  
Nigel Andrew Hibberts ◽  
Andrew Stewart Irving Loudon ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Cervus Elaphus ◽  
Hair Growth ◽  
Red Deer ◽  
Dermal Papilla ◽  
Hair Follicles ◽  
Dermal Papilla Cells ◽  
Cells Cultured

scholarly journals Hair Growth Activity of Three Plants of the Polynesian Cosmetopoeia and Their Regulatory Effect on Dermal Papilla Cells

Molecules ◽  
2020 ◽  
Vol 25 (19) ◽  
pp. 4360
Author(s):  
Kristelle Hughes ◽  
Raimana Ho ◽  
Stéphane Greff ◽  
Edith Filaire ◽  
Edwige Ranouille ◽  
...  
Keyword(s):  
Hair Loss ◽  
Hair Growth ◽  
Dermal Papilla ◽  
Hair Cycle ◽  
Bidens Pilosa ◽  
Dermal Papilla Cells ◽  
Qpcr Analysis ◽  
Chemical Content ◽  
Growth Activity ◽  
Gene Expression Levels

Hair loss is becoming increasingly prevalent as dietary and living habits change. The search for natural products to limit hair loss has led to tapping into traditional cosmetic knowledge. We studied three plants of the Polynesian cosmetopoeia, Bidens pilosa, Calophyllum inophyllum and Fagraea berteroana, to determine their ability to promote hair growth. Their chemical content was characterized by liquid chromatography coupled to mass spectrometry (LC-MS). Their proliferative activity on dermal papilla cells (DPCs) was assessed via MTT assay and molecular targets were evaluated by RT-qPCR analysis of seven factors involved in the modulation of the hair cycle, CCND1, LEF1, DKK1, WNT5A PPARD, TGFΒ1, PPARD and RSPO2. Our results show that our extracts significantly increased proliferation of dermal papilla cells. Furthermore, LC-MS/MS analysis revealed a diversity of molecules, flavonoids, iridoids and organic acids, some known for hair-inducing properties. Finally, specific extracts and fractions of all three plants either upregulated CCND1, LEF1 and PPARD involved in stimulating hair follicle proliferation and/or lowered the gene expression levels of hair growth inhibiting factors, DKK1 and TGFB1. Our findings suggest that extracts from B. pilosa, C. inophyllum and F. berteroana are interesting candidates to stimulate hair growth.

scholarly journals Dermal exosomes containing miR-218-5p promote hair regeneration by regulating β-catenin signaling

2020 ◽  
Vol 6 (30) ◽  
pp. eaba1685 ◽  
Author(s):  
Shiqi Hu ◽  
Zhenhua Li ◽  
Halle Lutz ◽  
Ke Huang ◽  
Teng Su ◽  
...  
Keyword(s):  
Hair Follicle ◽  
Hair Growth ◽  
Dermal Papilla ◽  
Hair Follicles ◽  
Hair Cycle ◽  
Paracrine Signaling ◽  
Hair Regrowth ◽  
Study Results ◽  
Anagen Phase ◽  
Hair Follicle Cycle

The progression in the hair follicle cycle from the telogen to the anagen phase is the key to regulating hair regrowth. Dermal papilla (DP) cells support hair growth and regulate the hair cycle. However, they gradually lose key inductive properties upon culture. DP cells can partially restore their capacity to promote hair regrowth after being subjected to spheroid culture. In this study, results revealed that DP spheroids are effective at inducing the progression of the hair follicle cycle from telogen to anagen compared with just DP cell or minoxidil treatment. Because of the importance of paracrine signaling in this process, secretome and exosomes were isolated from DP cell culture, and their therapeutic efficacies were investigated. We demonstrated that miR-218-5p was notably up-regulated in DP spheroid–derived exosomes. Western blot and immunofluorescence imaging were used to demonstrate that DP spheroid–derived exosomes up-regulated β-catenin, promoting the development of hair follicles.

scholarly journals Plakoglobin Suppresses Epithelial Proliferation and Hair Growth in Vivo

2000 ◽  
Vol 149 (2) ◽  
pp. 503-520 ◽  
Author(s):  
Emmanuelle Charpentier ◽  
Robert M. Lavker ◽  
Elizabeth Acquista ◽  
Pamela Cowin
Keyword(s):  
Hair Growth ◽  
Cultured Cells ◽  
Hair Follicles ◽  
Tumor Formation ◽  
Hair Cycle ◽  
Epithelial Proliferation ◽  
Desmosomal Cadherins ◽  
Hair Follicle Cycle

Plakoglobin regulates cell adhesion by providing a modulatable connection between both classical and desmosomal cadherins and their respective cytoskeletal linker proteins. Both plakoglobin and the related protein β-catenin are posttranscriptionally upregulated in response to Wnt-1 in cultured cells. Upregulation of β-catenin has been implicated in potentiating hyperproliferation and tumor formation. To investigate the role of plakoglobin in these functions we expressed a full-length (PG) and an NH2-terminally truncated form of plakoglobin (ΔN80PG) in mouse epidermis and hair follicles, tissues which undergo continuous and easily observed postnatal renewal and remodeling. Expression of these constructs results in stunted hair growth, a phenotype that has also been observed in transgenic mice expressing Wnt3 and Dvl2 (Millar et al. 1999). Hair follicles from PG and ΔN80PG mice show premature termination of the growth phase (anagen) of the hair cycle, an event that is regulated in part by FGF5 (Hebert et al. 1994). The proliferative rate of the epidermal cells was reduced and apoptotic changes, which are associated with entry into the regressive phase of the hair follicle cycle (catagen), occurred earlier than usual.

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