scholarly journals Transglutaminase 3: The Involvement in Epithelial Differentiation and Cancer

Cells ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 1996 ◽  
Author(s):  
Elina S. Chermnykh ◽  
Elena V. Alpeeva ◽  
Ekaterina A. Vorotelyak
Keyword(s):  
Hair Follicle ◽  
Human Tumor ◽  
Hair Shaft ◽  
Hair Follicles ◽  
Epidermal Keratinocytes ◽  
Macromolecular Complexes ◽  
Tumor Pathology ◽  
Keratin Intermediate Filaments ◽  
Transglutaminase 3

Transglutaminases (TGMs) contribute to the formation of rigid, insoluble macromolecular complexes, which are essential for the epidermis and hair follicles to perform protective and barrier functions against the environment. During differentiation, epidermal keratinocytes undergo structural alterations being transformed into cornified cells, which constitute a highly tough outermost layer of the epidermis, the stratum corneum. Similar processes occur during the hardening of the hair follicle and the hair shaft, which is provided by the enzymatic cross-linking of the structural proteins and keratin intermediate filaments. TGM3, also known as epidermal TGM, is one of the pivotal enzymes responsible for the formation of protein polymers in the epidermis and the hair follicle. Numerous studies have shown that TGM3 is extensively involved in epidermal and hair follicle physiology and pathology. However, the roles of TGM3, its substrates, and its importance for the integument system are not fully understood. Here, we summarize the main advances that have recently been achieved in TGM3 analyses in skin and hair follicle biology and also in understanding the functional role of TGM3 in human tumor pathology as well as the reliability of its prognostic clinical usage as a cancer diagnosis biomarker. This review also focuses on human and murine hair follicle abnormalities connected with TGM3 mutations.

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.

Activation of the Notch pathway in the hair cortex leads to aberrant differentiation of the adjacent hair-shaft layers

Development ◽  
2000 ◽  
Vol 127 (11) ◽  
pp. 2421-2432 ◽  
Author(s):  
M.H. Lin ◽  
C. Leimeister ◽  
M. Gessler ◽  
R. Kopan
Keyword(s):  
Transgenic Mice ◽  
Hair Follicle ◽  
Active Form ◽  
Notch Pathway ◽  
Dermal Papilla ◽  
Cell Types ◽  
Hair Shaft ◽  
Hair Follicles ◽  
Hair Cortex

Little is known about the mechanisms underlying the generation of various cell types in the hair follicle. To investigate the role of the Notch pathway in this process, transgenic mice were generated in which an active form of Notch1 (Notch(DeltaE)) was overexpressed under the control of the mouse hair keratin A1 (MHKA1) promoter. MHKA-Notch(DeltaE) is expressed only in one precursor cell type of the hair follicle, the cortex. Transgenic mice could be easily identified by the phenotypes of curly whiskers and wavy, sheen pelage hair. No effects of activated Notch on proliferation were detected in hair follicles of the transgenic mice. We find that activating Notch signaling in the cortex caused abnormal differentiation of the medulla and the cuticle, two neighboring cell types that did not express activated Notch. We demonstrate that these non-autonomous effects are likely caused by cell-cell interactions between keratinocytes within the hair follicle and that Notch may function in such interactions either by directing the differentiation of follicular cells or assisting cells in interpreting a gradient emanating from the dermal papilla.

scholarly journals Localisation and regulation of cholesterol transporters in the human hair follicle: mapping changes across the hair cycle

2021 ◽  
Author(s):  
Megan A. Palmer ◽  
Eleanor Smart ◽  
Iain S. Haslam
Keyword(s):  
Hair Follicle ◽  
Human Hair ◽  
Vital Role ◽  
Transport Proteins ◽  
Hair Follicles ◽  
Regulatory Control ◽  
Cholesterol Transport ◽  
Hair Cycle ◽  
Human Hair Follicle

AbstractCholesterol has long been suspected of influencing hair biology, with dysregulated homeostasis implicated in several disorders of hair growth and cycling. Cholesterol transport proteins play a vital role in the control of cellular cholesterol levels and compartmentalisation. This research aimed to determine the cellular localisation, transport capability and regulatory control of cholesterol transport proteins across the hair cycle. Immunofluorescence microscopy in human hair follicle sections revealed differential expression of ATP-binding cassette (ABC) transporters across the hair cycle. Cholesterol transporter expression (ABCA1, ABCG1, ABCA5 and SCARB1) reduced as hair follicles transitioned from growth to regression. Staining for free cholesterol (filipin) revealed prominent cholesterol striations within the basement membrane of the hair bulb. Liver X receptor agonism demonstrated active regulation of ABCA1 and ABCG1, but not ABCA5 or SCARB1 in human hair follicles and primary keratinocytes. These results demonstrate the capacity of human hair follicles for cholesterol transport and trafficking. Future studies examining the role of cholesterol transport across the hair cycle may shed light on the role of lipid homeostasis in human hair disorders.

scholarly journals The Role of Extracellular Vesicles in Cutaneous Remodeling and Hair Follicle Dynamics

2019 ◽  
Vol 20 (11) ◽  
pp. 2758 ◽  
Author(s):  
Elisa Carrasco ◽  
Gonzalo Soto-Heredero ◽  
María Mittelbrunn
Keyword(s):  
Hair Follicle ◽  
Extracellular Vesicles ◽  
Cell Function ◽  
Hair Follicles ◽  
The Body ◽  
Epithelial Stem Cells ◽  
Therapeutic Approaches ◽  
Waste Products ◽  
Efficient Treatment

Extracellular vesicles (EVs), including exosomes, microvesicles, and apoptotic bodies, are cell-derived membranous structures that were originally catalogued as a way of releasing cellular waste products. Since the discovery of their function in intercellular communication as carriers of proteins, lipids, and DNA and RNA molecules, numerous therapeutic approaches have focused on the use of EVs, in part because of their minimized risk compared to cell-based therapies. The skin is the organ with the largest surface in the body. Besides the importance of its body barrier function, much attention has been paid to the skin in regenerative medicine because of its cosmetic aspect, which is closely related to disorders affecting pigmentation and the presence or absence of hair follicles. The use of exosomes in therapeutic approaches for cutaneous wound healing has been reported and is briefly reviewed here. However, less attention has been paid to emerging interest in the potential capacity of EVs as modulators of hair follicle dynamics. Hair follicles are skin appendices that mainly comprise an epidermal and a mesenchymal component, with the former including a major reservoir of epithelial stem cells but also melanocytes and other cell types. Hair follicles continuously cycle, undergoing consecutive phases of resting, growing, and regression. Many biomolecules carried by EVs have been involved in the control of the hair follicle cycle and stem cell function. Thus, investigating the role of either naturally produced or therapeutically delivered EVs as signaling vehicles potentially involved in skin homeostasis and hair cycling may be an important step in the attempt to design future strategies towards the efficient treatment of several skin disorders.

scholarly journals Dicer- and BSC-dependent miRNAs during murine anagen development

2020 ◽  
Author(s):  
Neda Vishlaghi ◽  
Thomas S. Lisse
Keyword(s):  
Hair Follicle ◽  
Functional Role ◽  
Rna Binding ◽  
Mouse Skin ◽  
Mature Mirnas ◽  
Hair Follicles ◽  
Conditional Knockout ◽  
Follicle Cells ◽  
Epidermal Keratinocytes ◽  
Wide Range

AbstractMicroRNAs (miRNAs) are a major class of conserved non-coding RNAs that have a wide range of functions during development and disease. Biogenesis of canonical miRNAs depend on the cytoplasmic processing of pre-miRNAs to mature miRNAs by the Dicer endoribonuclease. Once mature miRNAs are generated, the miRNA-induced silencing complex, or miRISC, incorporates one strand of miRNAs as a template for recognizing complementary target messenger RNAs (mRNAs) to dictate post-transcriptional gene expression. Besides regulating miRNA biogenesis, Dicer is also part of miRISC to assist in activation of the complex. Dicer associates with other regulatory miRISC co-factors such as trans-activation responsive RNA-binding protein (Tarbp2) to regulate miRNA-based RNA interference. Although the functional role of miRNAs within epidermal keratinocytes have been extensively studied within embryonic and post-natal mouse skin, its contribution to the normal function of hair follicle bulge stem cells (BSCs) during post-natal hair follicle development is unknown. With this question in mind, we sought to ascertain whether Dicer-Tarpb2 plays a functional role within BSCs during induced anagen development by utilizing conditional knockout mouse models. Our findings suggest that Dicer, but not Tarbp2, functions within BSCs to regulate induced anagen (growth) development of post-natal hair follicles. These findings strengthen our understanding of miRNA-dependency within hair follicle cells to define a boundary for post-transcriptional gene regulation during anagen development.

scholarly journals Determination of the pH Gradient in Hair Follicles of Human Volunteers Using pH-Sensitive Melamine Formaldehyde-Pyranine Nile Blue Microparticles

Sensors ◽  
2020 ◽  
Vol 20 (18) ◽  
pp. 5243 ◽  
Author(s):  
Dennis Kaden ◽  
Lars Dähne ◽  
Fanny Knorr ◽  
Heike Richter ◽  
Jürgen Lademann ◽  
...  
Keyword(s):  
Hair Follicle ◽  
Laser Scanning ◽  
Nile Blue ◽  
Hair Shaft ◽  
Hair Follicles ◽  
Laser Scanning Microscopy ◽  
Confocal Laser ◽  
Melamine Formaldehyde

Nanoparticles can be applied to the hair follicles, which can serve as reservoirs for triggered drug release. A valid measurement method for the determination of the pH within the hair follicle in vivo has not been shown yet. Here, melamine formaldehyde particles up to 9 µm in size were applied on 40 freshly plucked scalp hairs of eight individuals to determine the pH along the hair shaft down to the root area of the hair. For fluorescent pH indicators, pyranine and Nile blue were incorporated into the particles. Measurements were conducted using confocal laser scanning microscopy. A pH decay gradient could be found from the hair sheath towards the external hair shaft (p = 0.012) with pH values at the hair sheath of 6.63 ± 0.09, at the hair sheath end at 6.33 ± 0.11, and at the external hair shaft at 6.17 ± 0.09 (mean ± SE). The pH difference between the hair sheath end and the external hair shaft was found to be significant (p = 0.036). The results might be comparable with the pH within the hair follicle in vivo indicating a pH increase towards the hair root.

The effect of IGF-I on the growth of secondary hair follicles of the Cashmere goat in vitro

1997 ◽  
Vol 1997 ◽  
pp. 170-170
Author(s):  
H. Galbraith ◽  
D. Sims ◽  
D. Hazlerigg
Keyword(s):  
Growth Factors ◽  
Hair Follicle ◽  
Human Hair ◽  
Hair Follicles ◽  
Cashmere Goat ◽  
Igf I ◽  
Hair Follicle Cycle ◽  
Insulin Like Growth Factors

Factors regulating the growth of Cashmere fibre and the hair follicle cycle are poorly understood. Insulin-like growth factors (IGFs) or insulin at higher concentrations, have been shown to stimulate in vitro growth of human hair follicles (Philpott et al, 1994). The role of such mitogens in the production of cashmere fibre by the Cashmere goat has not been previously investigated. The objective the study reported here was to investigate the growth of hair follicles in the absence and presence of insulin or IGF-I using our established in vitro technique.

scholarly journals The role of cathepsin E in terminal differentiation of keratinocytes

2011 ◽  
Vol 392 (6) ◽  
Author(s):  
Tomoyo Kawakubo ◽  
Atsushi Yasukochi ◽  
Kuniaki Okamoto ◽  
Yoshiko Okamoto ◽  
Seiji Nakamura ◽  
...  
Keyword(s):  
Hair Follicle ◽  
Primary Cultures ◽  
Terminal Differentiation ◽  
Epidermal Differentiation ◽  
Keratinocyte Differentiation ◽  
Epidermal Keratinocytes ◽  
Marker Genes ◽  
Differentiation Markers ◽  
Cathepsin E

Abstract Cathepsin E (CatE) is predominantly expressed in the rapidly regenerating gastric mucosal cells and epidermal keratinocytes, in addition to the immune system cells. However, the role of CatE in these cells remains unclear. Here we report a crucial role of CatE in keratinocyte terminal differentiation. CatE deficiency in mice induces abnormal keratinocyte differentiation in the epidermis and hair follicle, characterized by the significant expansion of corium and the reduction of subcutaneous tissue and hair follicle. In a model of skin papillomas formed in three different genotypes of syngeneic mice, CatE deficiency results in significantly reduced expression and altered localization of the keratinocyte differentiation induced proteins, keratin 1 and loricrin. Involvement of CatE in the regulation of the expression of epidermal differentiation specific proteins was corroborated by in vitro studies with primary cultures of keratinocytes from the three different genotypes of mice. In wild-type keratinocytes after differentiation inducing stimuli, the CatE expression profile was compatible to those of the terminal differentiation marker genes tested. Overexpression of CatE in mice enhances the keratinocyte terminal differentiation process, whereas CatE deficiency results in delayed differentiation accompanying the reduced expression or the ectopic localization of the differentiation markers. Our findings suggest that in keratinocytes CatE is functionally linked to the expression of terminal differentiation markers, thereby regulating epidermis formation and homeostasis.

scholarly journals Hair Regrowth with Cannabidiol (CBD)-rich Hemp Extract – A Case Series

Cannabis ◽  
2021 ◽  
Vol 4 (1) ◽  
pp. 53-59
Author(s):  
Gregory Smith ◽  
John Satino
Keyword(s):  
Hair Follicle ◽  
Synergistic Effects ◽  
Case Series ◽  
Endocannabinoid System ◽  
Follicle Cell ◽  
Hair Shaft ◽  
Hair Follicles ◽  
Vanilloid Receptor ◽  
Follicle Cells ◽  
Better Than

Androgenetic alopecia (AGA) is the most common cause of hair loss. Several FDA approved medications are available but offer limited results. Studies have shown that the endocannabinoid system (ECS) is a key player in hair follicle cell growth. The ECS cannabinoid type one (CB1) receptors are well expressed in the hair follicle cells. Cannabidiol CBD is a negative allosteric modulator of the CB1 receptor and has been shown to result in hair shaft elongation. In addition, the hair follicle cycle phases are controlled by the ECS vanilloid receptor-1 (TRPV1). CBD has also been shown to increase Wnt signaling pathways that are involved in the differentiation of dermal progenitor cells into new hair follicles and maintaining the anagen phase of the hair cycle. The effects of CBD on hair growth are dose dependent and higher doses may result in premature entry into the catagen phase via a receptor known as vanilloid receptor-4 (TRPV4). Topical application of CBD reaches hair follicles where it is a CB1 negative modulator, and TRPV1, and TRPV4 agonist. A study was done of 35 subjects with AGA using a once daily topical hemp oil formulation, averaging about 3-4 mg per day of CBD and minimal amounts of other cannabinoids for six months. A hair count of the greatest area of alopecia was carried out before treatment and again after six months. The results revealed that men did slightly better than women, and the vertex area did better than the temporal areas. On average there was statistically significant 93.5% increase in hair after 6 months. All subjects had some regrowth. There were no reported adverse effects. Since the CBD works through novel mechanisms different from finasteride and minoxidil it can be used in conjunction with these current drugs and would be expected to have synergistic effects.

Human hair growth in vitro

1990 ◽  
Vol 97 (3) ◽  
pp. 463-471
Author(s):  
M.P. Philpott ◽  
M.R. Green ◽  
T. Kealey
Keyword(s):  
Hair Follicle ◽  
Human Hair ◽  
Subcutaneous Fat ◽  
Hair Shaft ◽  
Hair Follicles ◽  
Anagen Hair ◽  
Scalpel Blade ◽  
Thymidine Autoradiography

We report for the first time the successful maintenance and growth of human hair follicles in vitro. Human anagen hair follicles were isolated by microdissection from human scalp skin. Isolation of the hair follicles was achieved by cutting the follicle at the dermo-subcutaneous fat interface using a scalpel blade. Intact hair follicles were then removed from the fat using watchmakers' forceps. Isolated hair follicles maintained free-floating in supplemented Williams E medium in individual wells of 24-well multiwell plates showed a significant increase in length over 4 days. The increase in length was seen to be attributed to the production of a keratinised hair shaft, and was not associated with the loss of hair follicle morphology. [methyl-3H]thymidine autoradiography confirmed that in vitro the in vivo pattern of DNA synthesis was maintained; furthermore, [35S]methionine labelling of keratins showed that their patterns of synthesis did not change with maintenance. The importance of this model to hair follicle biology is further demonstrated by the observations that TGF-beta 1 has a negative growth-regulatory effect on hair follicles in vitro and that EGF mimics the in vivo depilatory effects that have been reported in sheep and mice.

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