scholarly journals The Effect of JAK Inhibitor on the Survival, Anagen Re-Entry, and Hair Follicle Immune Privilege Restoration in Human Dermal Papilla Cells

2020 ◽  
Vol 21 (14) ◽  
pp. 5137
Author(s):  
Jung Eun Kim ◽  
Yu Jin Lee ◽  
Hye Ree Park ◽  
Dong Geon Lee ◽  
Kwan Ho Jeong ◽  
...  
Keyword(s):  
Growth Factors ◽  
Hair Follicle ◽  
Dermal Papilla ◽  
Immune Privilege ◽  
Jak Inhibitors ◽  
Dermal Papilla Cells ◽  
Ifn Γ ◽  
Vitro Model ◽  
Stat Pathway

Topical or systemic administration of JAK inhibitors has been shown to be a new treatment modality for severe alopecia areata (AA). Some patients show a good response to JAK inhibitors, but frequently relapse after cessation of the treatment. There have been no guidelines about the indications and use of JAK inhibitors in treating AA. The basic pathomechanism of AA and the relevant role of JAK inhibitors should support how to efficiently use JAK inhibitors. We sought to investigate the effect of JAK1/2 inhibitor on an in vitro model of AA and to examine the possible mechanisms. We used interferon gamma-pretreated human dermal papilla cells (hDPCs) as an in vitro model of AA. Ruxolitinib was administered to the hDPCs, and cell viability was assessed. The change of expression of the Wnt/β-catenin pathway, molecules related to the JAK-STAT pathway, and growth factors in ruxolitinib-treated hDPCs was also examined by reverse transcription PCR and Western blot assay. We examined immune-privilege-related molecules by immunohistochemistry in hair-follicle culture models. Ruxolitinib did not affect the cell viability of the hDPCs. Ruxolitinib activated several molecules in the Wnt/β-catenin signaling pathway, including Lef1 and β-catenin, and suppressed the transcription of DKK1 in hDPCs, but not its translation. Ruxolitinib reverted IFN-γ-induced expression of caspase-1, IL-1β, IL-15, and IL-18, and stimulated several growth factors, such as FGF7. Ruxolitinib suppressed the phosphorylation of JAK1, JAK2 and JAK3, and STAT1 and 3 compared to IFN-γ pretreated hDPCs. Ruxolitinib pretreatment showed a protective effect on IFN-γ-induced expression of MHC-class II molecules in cultured hair follicles. In conclusion, ruxolitinib modulated and reverted the interferon-induced inflammatory changes by blocking the JAK-STAT pathway in hDPCs under an AA-like environment. Ruxolitinib directly stimulated anagen-re-entry signals in hDPCs by affecting the Wnt/β-catenin pathway and promoting growth factors in hDPCs. Ruxolitinib treatment prevented IFN-γ-induced collapse of hair-follicle immune privilege.

scholarly journals Establishment of 3D Spheroid Human Dermal Papilla Cells as an Effective Model for Hair Growth Screening Compounds Compared with the 2D System: An Example of Minoxidil and 3,4,5-Tri-O-caffeoylquinic acid (TCQA)

2021 ◽  
Author(s):  
Meriem Bejaoui ◽  
Aprill Kee Oliva ◽  
May Sin Ke ◽  
Farhana Ferdousi ◽  
Hiroko Isoda
Keyword(s):  
Hair Follicle ◽  
Hair Growth ◽  
In Vitro Model ◽  
3D Model ◽  
Dermal Papilla ◽  
Dermal Papilla Cells ◽  
Caffeoylquinic Acid ◽  
Vitro Model

Abstract IntroductionDermal papilla cells (DPc) is an important element in studying the hair follicle (HF) niche. The human hair follicle dermal papilla cells (HFDPC) are widely used as an in vitro model to study hair growth related research. These cells are usually grown in 2D culture, nevertheless, this system did not show efficient therapeutic effect on HF regeneration and growth, and key differences were observed between cell activity in vitro and in vivo. ObjectiveRecent studies have showed that HFDPC grown in 3D hanging spheroids is more morphologically akin to intact DPc microenvironment. This current study showed that the 3D model is applicable to the commercial cell line with new insights on its variability by comparing to previous studies of gene signature restored by 3D culture.Methods and Results Our data demonstrated that HFDPCS grown in 3D in vitro model can influence not only hair growth-related pathways but also immune system -related pathways compared to 2D cell monolayer. Furthermore, we compared the expression of signalling molecules and metabolism-associated proteins of HFDPC in minoxidil (FDA approved drug for hair loss treatment) and 3,4,5-tri-O-caffeoylquinic acid (TCQA) (recently found to induce hair growth in vitro and in vivo) treated 3D and 2D cell cultures using microarray analysis. Conclusion Further validation of the results confirms the suitability of this cell line for 3D model while providing new insights such as to the mechanisms behind the hair growth effects of 3D spheroid treated with hair growth promoting agents.

Smooth muscle alpha-actin is a marker for hair follicle dermis in vivo and in vitro

1991 ◽  
Vol 99 (3) ◽  
pp. 627-636 ◽  
Author(s):  
C.A. Jahoda ◽  
A.J. Reynolds ◽  
C. Chaponnier ◽  
J.C. Forester ◽  
G. Gabbiani
Keyword(s):  
Smooth Muscle ◽  
Hair Follicle ◽  
Dermal Papilla ◽  
Hair Follicles ◽  
Dermal Papilla Cells ◽  
Smooth Muscle Alpha Actin ◽  
Actin Expression ◽  
Alpha Actin ◽  
Sheath Cells

We have examined the expression of smooth muscle alpha-actin in hair follicles in situ, and in hair follicle dermal cells in culture by means of immunohistochemistry. Smooth muscle alpha-actin was present in the dermal sheath component of rat vibrissa, rat pelage and human follicles. Dermal papilla cells within all types of follicles did not express the antigen. However, in culture a large percentage of both hair dermal papilla and dermal sheath cells were stained by this antibody. The same cells were negative when tested with an antibody to desmin. Overall, explant-derived skin fibroblasts had relatively low numbers of positively marked cells, but those from skin regions of high hair-follicle density displayed more smooth muscle alpha-actin expression than fibroblasts from areas with fewer follicles. 2-D SDS-PAGE confirmed that, unlike fibroblasts, cultured papilla cells contained significant quantities of the alpha-actin isoform. The rapid switching on of smooth muscle alpha-actin expression by dermal papilla cells in early culture, contrasts with the behaviour of smooth muscle cells in vitro, and has implications for control of expression of the antigen in normal adult systems. The very high percentage of positively marked cultured papilla and sheath cells also provides a novel marker of cells from follicle dermis, and reinforces the idea that they represent a specialized cell population, contributing to the heterogeneity of fibroblast cell types in the skin dermis, and possibly acting as a source of myofibroblasts during wound healing.

Apoptosis of the dermal papilla cells of hair follicle associated with the expression of gene HSPCO16 in vitro

2005 ◽  
Vol 14 (3) ◽  
pp. 209-214 ◽  
Author(s):  
Wei B. Yang ◽  
Fei Hao ◽  
Zhi Q. Song ◽  
Xi C. Yang ◽  
Bing Ni
Keyword(s):  
Hair Follicle ◽  
Dermal Papilla ◽  
Dermal Papilla Cells

scholarly journals Detection of Functionally Active Melanocortin Receptors and Evidence for an Immunoregulatory Activity of α-Melanocyte-Stimulating Hormone in Human Dermal Papilla Cells

Endocrinology ◽  
2005 ◽  
Vol 146 (11) ◽  
pp. 4635-4646 ◽  
Author(s):  
Markus Böhm ◽  
Mareike Eickelmann ◽  
Zhuo Li ◽  
Stefan W. Schneider ◽  
Vinzenz Oji ◽  
...  
Keyword(s):  
Hair Follicle ◽  
Inflammatory Responses ◽  
Dermal Papilla ◽  
Intercellular Adhesion Molecule ◽  
Regulatory Function ◽  
Intracellular Camp ◽  
Intercellular Adhesion Molecule 1 ◽  
Dermal Papilla Cells ◽  
Signaling Protein

Proopiomelanocortin (POMC)-derived peptides and their receptors have been identified in many peripheral organs including the skin in which they exert a diversity of biological actions. We investigated the expression and potential role of the POMC system in human dermal papilla cells (DPCs), a specialized cutaneous mesenchymal cell type regulating hair follicle activity. In culture, these cells expressed POMC and displayed immunoreactivity for ACTH, αMSH, and β-endorphin. Among the prohormone convertases (PCs) tested, only PC2, its chaperone 7B2, and furin convertase but not PC1 and paired basic amino acid cleaving enzyme 4 gene were detected. Human DPCs in vitro expressed both the melanocortin-1 receptor (MC-1R) and MC-4R, and immunoreactivity for these receptors was also present in cells of the human dermal papilla in situ. In contrast to the dermal papilla of agouti mice, agouti signaling protein, a natural and highly selective MC-1R and MC-4R antagonist, was undetectable in human DPCs. The MC-Rs detected in human DPCs were functionally active because αMSH increased intracellular cAMP and calcium. Preincubation of the cells with a synthetic peptide corresponding to the C-terminal domain of agouti signaling protein abrogated cAMP induction by αMSH. Furthermore, αMSH was capable of antagonizing the expression of intercellular adhesion molecule-1 induced by the proinflammatory cytokine interferon-γ. Our data suggest a regulatory function of αMSH within the dermal papilla whose disruption may lead to deregulation of immune and inflammatory responses of the hair follicle, thereby possibly contributing to the development of inflammatory forms of alopecia.

scholarly journals Mesenchymal Stem Cells Antagonize IFN-Induced Proinflammatory Changes and Growth Inhibition Effects via Wnt/β-Catenin and JAK/STAT Pathway in Human Outer Root Sheath Cells and Hair Follicles

2021 ◽  
Vol 22 (9) ◽  
pp. 4581
Author(s):  
Yu-Jin Lee ◽  
Song-Hee Park ◽  
Hye-Ree Park ◽  
Young Lee ◽  
Hoon Kang ◽  
...  
Keyword(s):  
Stem Cells ◽  
In Vitro Model ◽  
Outer Root Sheath ◽  
Root Sheath ◽  
Ifn Γ ◽  
Vitro Model ◽  
And Migration ◽  
Outer Root Sheath Cells ◽  
Stat Pathway

Mesenchymal stem cell therapy (MSCT) has been shown to be a new therapeutic option for treating alopecia areata (AA). Outer root sheath cells (ORSCs) play key roles in maintaining the hair follicle structure and supporting the bulge area. In human ORSCs (hORSCs), the mechanism for this process has not been extensively studied. In this study, we aimed to examine the influence of human hematopoietic mesenchymal stem cells (hHMSCs) in the hORSCs in vitro model of AA and determine the mechanisms controlling efficacy. Interferon-gamma (IFN-γ) pretreatment was used to induce an in vitro model of AA in hORSCs. The effect of MSCT on the viability and migration of hORSCs was examined using co-cultures, the MTT assay, and migration assays. We investigated the expression of molecules related to the Wnt/β-catenin pathway, JAK/STAT pathway, and growth factors in hHMSC-treated hORSCs by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analyses. hHMSCs increased hORSC viability and migration when they were co-cultured. hHMSCs reverted IFN-γ-induced expression—including NLRP3, ASC, caspase-1, CXCL-9 through 11, IL-1β, and IL-15—and upregulated several growth factors and hair stem cell markers. hHMSCs activated several molecules in the Wnt/β-catenin signaling pathway, such as in the Wnt families, β-catenin, phosphorylated GSK-3β and cyclin D1, and suppressed the expression of DKK1 induced by IFN-γ in hORSCs. hHMSCs suppressed the phosphorylation of JAK1 to 3, STAT1, and STAT3 compared to the controls and IFN-γ-pretreated hORSCs. These results demonstrate that hHMSCs increased hORSC viability and migration in the in vitro AA model. Additionally, MSCT definitely stimulated anagen survival and hair growth in an HF organ culture model. MSCT appeared to be associated with the Wnt/β-catenin and JAK/STAT pathways in hORSCs.

scholarly journals Hair follicle germs containing vascular endothelial cells for hair regenerative medicine

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Tatsuto Kageyama ◽  
Yang-Sook Chun ◽  
Junji Fukuda
Keyword(s):  
Endothelial Cells ◽  
Regenerative Medicine ◽  
Hair Follicle ◽  
Vascular Endothelial Cells ◽  
Morphological Characteristics ◽  
Dermal Papilla ◽  
Hair Follicles ◽  
Vascular Endothelial ◽  
Dermal Papilla Cells

AbstractHair regenerative medicine has emerged as a promising approach for the treatment of severe hair loss. Recent advances in three-dimensional tissue engineering, such as formation of hair follicle germs (HFGs), have considerably improved hair regeneration after transplantation in animal models. Here, we proposed an approach for fabricating HFGs containing vascular endothelial cells. Epithelial, dermal papilla, and vascular endothelial cells initially formed a single aggregate, which subsequently became a dumbbell-shaped HFG, wherein the vascular endothelial cells localized in the region of dermal papilla cells. The HFGs containing vascular endothelial cells exhibited higher expression of hair morphogenesis-related genes in vitro, along with higher levels of hair shaft regeneration upon transplantation to the dorsal side of nude mice, than those without vascular endothelial cells. The generated hair follicles represented functional characteristics, such as piloerection, as well as morphological characteristics comparable to those of natural hair shafts. This approach may provide a promising strategy for fabricating tissue grafts with higher hair inductivity for hair regenerative medicine.

scholarly journals Transcriptome Profiling of Human Follicle Dermal Papilla Cells in response to Porphyra-334 Treatment by RNA-Seq

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Su Yeon Kim ◽  
Won Kyong Cho ◽  
Hye-In Kim ◽  
Seung Hye Paek ◽  
Sung Joo Jang ◽  
...  
Keyword(s):  
Hair Follicle ◽  
Transcriptome Profiling ◽  
Dermal Papilla ◽  
Clinical Test ◽  
Dermal Papilla Cells ◽  
Epidermal Structure ◽  
Vitro Assay

Porphyra-334 is a kind of mycosporine-like amino acid absorbing ultraviolet-A. Here, we characterized porphyra-334 as a potential antiaging agent. An in vitro assay revealed that porphyra-334 dramatically promoted collagen synthesis in fibroblast cells. The effect of porphyra-334 on cell proliferation was dependent on the cell type, and the increase of cell viability by porphyra-334 was the highest in keratinocyte cells among the three tested cell types. An in vivo clinical test with 22 participants demonstrated the possible role of porphyra-334 in the improvement of periorbital wrinkles. RNA-sequencing using human follicle dermal papilla (HFDP) cells upon porphyra-334 treatment identified the upregulation of metallothionein- (MT-) associated genes, confirming the antioxidant role of porphyra-334 with MT. Moreover, the expression of genes involved in nuclear chromosome segregation and the encoding of components of kinetochores was upregulated by porphyra-334 treatment. Furthermore, we found that several genes associated with the hair follicle cycle, the hair follicle structure, the epidermal structure, and stem cells were upregulated by porphyra-334 treatment, suggesting the potential role of porphyra-334 in hair follicle growth and maintenance. In summary, we provided several new pieces of evidence of porphyra-334 as a potential antiaging cosmetic agent and elucidated the expression network in HFDP cells upon porphyra-334.

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