scholarly journals Rac1 Is Crucial for Hair Follicle Integrity but Is Not Essential for Maintenance of the Epidermis

2006 ◽  
Vol 26 (18) ◽  
pp. 6957-6970 ◽  
Author(s):  
Anna Chrostek ◽  
Xunwei Wu ◽  
Fabio Quondamatteo ◽  
Rong Hu ◽  
Anna Sanecka ◽  
...  
Keyword(s):  
Hair Follicle ◽  
Hair Follicles ◽  
Small Gtpase ◽  
Epidermal Keratinocytes ◽  
Sebaceous Glands ◽  
Cellular Processes ◽  
Normal Differentiation ◽  
Deficient Mice

ABSTRACT Rac1 is a small GTPase that regulates the actin cytoskeleton but also other cellular processes. To investigate the function of Rac1 in skin, we generated mice with a keratinocyte-restricted deletion of the rac1 gene. Rac1-deficient mice lost nearly all of their hair within a few weeks after birth. The nonpermanent part of mutant hair follicles developed constrictions; lost expression of hair follicle-specific keratins, E-cadherin, and α6 integrin; and was eventually removed by macrophages. The permanent part of hair follicles and the sebaceous glands were maintained, but no regrowth of full-length hair follicles was observed. In the skin of mutant mice, epidermal keratinocytes showed normal differentiation, proliferation, cell-cell contacts, and basement membrane deposition, demonstrating no obvious defects of Rac1-deficient epidermis in vivo. In vitro, Rac1-null keratinocytes displayed a strong spreading defect and slightly impaired adhesion. These data show that Rac1 plays an important role in sustaining the integrity of the lower part of hair follicles but not in maintenance of the epidermis.

scholarly journals Interfollicular epidermal stem-like cells for the recreation of the hair follicle epithelial compartment

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Carla M. Abreu ◽  
Rogério P. Pirraco ◽  
Rui L. Reis ◽  
Mariana T. Cerqueira ◽  
Alexandra P. Marques
Keyword(s):  
Hair Follicle ◽  
Cell Sorting ◽  
Dermal Papilla ◽  
Epidermal Keratinocytes ◽  
Sebaceous Glands ◽  
Phenotypic Profile ◽  
Cell Source ◽  
Epithelial Compartment ◽  
The Ideal

Abstract Background Hair follicle (HF) development and growth are dependent on epithelial-mesenchymal interactions (EMIs). Dermal papilla (DP) cells are recognized as the key inductive mesenchymal player, but the ideal source of receptive keratinocytes for human HF regeneration is yet to be defined. We herein investigated whether human interfollicular epidermal keratinocytes with stem-like features (EpSlKCs), characterized by a α6bri/CD71dim expression, can replace human hair follicular keratinocytes (HHFKCs) for the recreation of the HF epithelium and respective EMIs. Methods The α6bri/CD71dim cellular fraction was selected from the whole interfollicular keratinocyte population through fluorescence-activated cell sorting and directly compared with follicular keratinocytes in terms of their proliferative capacity and phenotype. The crosstalk with DP cells was studied in an indirect co-culture system, and EpSlKC hair forming capacity tested in a hair reconstitution assay when combined with DP cells. Results EpSlKCs exhibited a phenotypic profile similar to follicular keratinocytes and were capable of increasing DP cell proliferation and, for short co-culture times, the number of alkaline phosphatase-active cells, suggesting an improvement of their inductivity. Moreover, the recreation of immature HFs and sebaceous glands was observed after EpSlKC and DP cell co-grafting in nude mice. Conclusions Our results suggest that EpSlKCs are akin to follicular keratinocytes and can crosstalk with DP cells, contributing to HF morphogenesis in vivo, thus representing an attractive epithelial cell source for hair regeneration strategies.

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 Disruption of Sept6, a Fusion Partner Gene of MLL, Does Not Affect Ontogeny, Leukemogenesis Induced by MLL-SEPT6, or Phenotype Induced by the Loss of Sept4

2005 ◽  
Vol 25 (24) ◽  
pp. 10965-10978 ◽  
Author(s):  
Ryoichi Ono ◽  
Masafumi Ihara ◽  
Hideaki Nakajima ◽  
Katsutoshi Ozaki ◽  
Yuki Kataoka-Fujiwara ◽  
...  
Keyword(s):  
Fusion Gene ◽  
Fusion Partner ◽  
Myeloproliferative Disease ◽  
Cellular Processes ◽  
Partner Gene ◽  
Quantitative Changes ◽  
High Degree ◽  
Deficient Mice

ABSTRACT Septins are evolutionarily conserved GTP-binding proteins that can heteropolymerize into filaments. Recent studies have revealed that septins are involved in not only diverse normal cellular processes but also the pathogenesis of various diseases, including cancer. SEPT6 is ubiquitously expressed in tissues and one of the fusion partner genes of MLL in the 11q23 translocations implicated in acute leukemia. However, the roles of this septin in vivo remain elusive. We have developed Sept6-deficient mice that exhibited neither gross abnormalities, changes in cytokinesis, nor spontaneous malignancy. Sept6 deficiency did not cause any quantitative changes in any of the septins evaluated in this study, nor did it cause any additional changes in the Sept4-deficient mice. Even the depletion of Sept11, a close homolog of Sept6, did not affect the Sept6-null cells in vitro, thus implying a high degree of redundancy in the septin system. Furthermore, a loss of Sept6 did not alter the phenotype of myeloproliferative disease induced by MLL-SEPT6, thus suggesting that Sept6 does not function as a tumor suppressor. To our knowledge, this is the first report demonstrating that a disruption of the translocation partner gene of MLL in 11q23 translocation does not contribute to leukemogenesis by the MLL fusion gene.

scholarly journals β-Catenin-Dependent and -Independent Effects of ΔN-Plakoglobin on Epidermal Growth and Differentiation

2004 ◽  
Vol 24 (19) ◽  
pp. 8649-8661 ◽  
Author(s):  
J. Teulière ◽  
M. M. Faraldo ◽  
M. Shtutman ◽  
W. Birchmeier ◽  
J. Huelsken ◽  
...  
Keyword(s):  
Hair Follicle ◽  
Intracellular Signaling ◽  
Target Genes ◽  
Glycogen Synthase ◽  
Mouse Skin ◽  
Hair Follicles ◽  
Epidermal Differentiation ◽  
Follicular Tumors

ABSTRACT Both β-catenin and plakoglobin can stimulate the expression of Lef/Tcf target genes in vitro. β-Catenin is known to associate with Lef/Tcf factors and to participate directly in transactivation in vivo, whereas the role of plakoglobin in transcriptional regulation has been less studied. To analyze the functions of plakoglobin in vivo, we generated transgenic mice expressing in the epidermis N-terminally truncated plakoglobin (ΔN122-PG) lacking the glycogen synthase kinase 3β phosphorylation sites and therefore protected against degradation (transgenic line K5-ΔN122-PG). The expression of ΔN122-PG led to the formation of additional hair germs, hyperplastic hair follicles, and noninvasive hair follicle tumors, a phenotype reminiscent of that induced by expression of N-terminally truncated β-catenin. However, if expressed in β-catenin-null epidermis, ΔN122-PG did not induce new hair follicle germs and follicular tumors. Thus, ΔN122-PG cannot substitute for β-catenin in its signaling functions in vivo and the phenotype observed in K5-ΔN122-PG mouse skin must be due to the aberrant activation of β-catenin signaling. On the other hand, the expression of ΔN122-PG in β-catenin-null skin significantly increased the survival rate of mutant mice, rescued differentiation, and limited excessive proliferation in the interfollicular epidermis, suggesting that plakoglobin may be involved in the intracellular signaling events essential for epidermal differentiation.

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.

scholarly journals Tp63-expressing adult epithelial stem cells cross lineages boundaries revealing latent hairy skin competence

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Stéphanie Claudinot ◽  
Jun-Ichi Sakabe ◽  
Hideo Oshima ◽  
Christèle Gonneau ◽  
Thimios Mitsiadis ◽  
...  
Keyword(s):  
Stem Cells ◽  
Transcription Factor ◽  
Hair Follicle ◽  
Hair Follicles ◽  
Epidermal Cells ◽  
Epithelial Stem Cells ◽  
Sebaceous Glands ◽  
Embryonic Origin ◽  
Lineage Markers

Abstract The formation of hair follicles, a landmark of mammals, requires complex mesenchymal–epithelial interactions and it is commonly believed that embryonic epidermal cells are the only cells that can respond to hair follicle morphogenetic signals in vivo. Here, we demonstrate that epithelial stem cells of non-skin origin (e.g. that of cornea, oesophagus, vagina, bladder, prostate) that express the transcription factor Tp63, a master gene for the development of epidermis and its appendages, can respond to skin morphogenetic signals. When exposed to a newborn skin microenvironment, these cells express hair-follicle lineage markers and contribute to hair follicles, sebaceous glands and/or epidermis renewal. Our results demonstrate that lineage restriction is not immutable and support the notion that all Tp63-expressing epithelial stem cells, independently of their embryonic origin, have latent skin competence explaining why aberrant hair follicles or sebaceous glands are sometimes observed in non-skin tissues (e.g. in cornea, vagina or thymus).

scholarly journals 12-hydroxyheptadecatrienoic acid promotes epidermal wound healing by accelerating keratinocyte migration via the BLT2 receptor

2014 ◽  
Vol 211 (6) ◽  
pp. 1063-1078 ◽  
Author(s):  
Min Liu ◽  
Kazuko Saeki ◽  
Takehiko Matsunobu ◽  
Toshiaki Okuno ◽  
Tomoaki Koga ◽  
...  
Keyword(s):  
Wound Healing ◽  
Wound Closure ◽  
Cultured Cells ◽  
Leukotriene B4 ◽  
Epidermal Keratinocytes ◽  
Skin Wound Healing ◽  
Wound Fluid ◽  
Deficient Mice

Leukotriene B4 (LTB4) receptor type 2 (BLT2) is a G protein–coupled receptor (GPCR) for 12(S)-hydroxyheptadeca-5Z,8E,10E-trienoic acid (12-HHT) and LTB4. Despite the well-defined proinflammatory roles of BLT1, the in vivo functions of BLT2 remain elusive. As mouse BLT2 is highly expressed in epidermal keratinocytes, we investigated the role of the 12-HHT/BLT2 axis in skin wound healing processes. 12-HHT accumulated in the wound fluid in mice, and BLT2-deficient mice exhibited impaired re-epithelialization and delayed wound closure after skin punching. Aspirin administration reduced 12-HHT production and resulted in delayed wound closure in wild-type mice, which was abrogated in BLT2-deficient mice. In vitro scratch assay using primary keratinocytes and a keratinocyte cell line also showed that the 12-HHT/BLT2 axis accelerated wound closure through the production of tumor necrosis factor α (TNF) and matrix metalloproteinases (MMPs). A synthetic BLT2 agonist accelerated wound closure in cultured cells as well as in C57BL/6J and diabetic mice. These results identify a novel mechanism underlying the action of the 12-HHT/BLT2 axis in epidermal keratinocytes and accordingly suggest the use of BLT2 agonists as therapeutic agents to accelerate wound healing, particularly for intractable wounds, such as diabetic ulcers.

scholarly journals Suppression of FGF5 and FGF18 Expression by Cholesterol-Modified siRNAs Promotes Hair Growth in Mice

2021 ◽  
Vol 12 ◽  
Author(s):  
Jungang Zhao ◽  
Haojie Lin ◽  
Lusheng Wang ◽  
Keke Guo ◽  
Rongrong Jing ◽  
...  
Keyword(s):  
Hair Follicle ◽  
Topical Application ◽  
Inhibitory Effect ◽  
Intradermal Injection ◽  
Hair Follicles ◽  
Anagen Phase ◽  
A Cell ◽  
Hair Follicle Cycle

FGF5 and FGF18 are key factors in the regulation of the hair follicle cycle. FGF5 is overexpressed during the late anagen phase and serves as a crucial regulatory factor that promotes the anagen-to-catagen transition in the hair follicle cycle. FGF18, which is overexpressed during the telogen phase, mainly regulates the hair follicle cycle by maintaining the telogen phase and inhibiting the entry of hair follicles into the anagen phase. The inhibition of FGF5 may prolong the anagen phase, whereas the inhibition of FGF18 may promote the transition of the hair follicles from the telogen phase to the anagen phase. In the present study, we used siRNA to suppress FGF5 or FGF18 expression as a way to inhibit the activity of these genes. Using qPCR, we showed that FGF5-targeting siRNA modified by cholesterol was more effective than the same siRNA bound to a cell-penetrating peptide at suppressing the expression of FGF5 both in vitro and in vivo. We then investigated the effects of the cholesterol-modified siRNA targeting either FGF5 or FGF18 on the hair follicle cycle in a depilated area of the skin on the back of mice. The cholesterol-modified siRNA, delivered by intradermal injection, effectively regulated the hair follicle cycle by inhibiting the expression of FGF5 and FGF18. More specifically, intradermal injection of a cholesterol-modified FGF5-targeted siRNA effectively prolonged the anagen phase of the hair follicles, whereas intradermal injection of the cholesterol-modified FGF18-targeted siRNA led to the mobilization of telogen follicles to enter the anagen phase earlier. The inhibitory effect of the cholesterol-modified FGF18-targeted siRNA on FGF18 expression was also evaluated for a topically applied siRNA. Topical application of a cream containing the cholesterol-modified FGF18-targeted siRNA on a depilated area of the skin of the back of mice revealed comparable inhibition of FGF18 expression with that observed for the same siRNA delivered by intradermal injection. These findings suggested that alopecia could be prevented and hair regrowth could be restored either through the intradermal injection of cholesterol-modified siRNA targeting FGF5 or FGF18 or the topical application of FGF18 siRNA.

scholarly journals Increased Expression of Zyxin and Its Potential Function in Androgenetic Alopecia

2021 ◽  
Vol 8 ◽  
Author(s):  
Qingmei Liu ◽  
Xiangguang Shi ◽  
Yue Zhang ◽  
Yan Huang ◽  
Kai Yang ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hair Follicle ◽  
Hair Growth ◽  
Ex Vivo ◽  
Cell Activity ◽  
Hair Follicles ◽  
Androgenetic Alopecia ◽  
Pcr Analysis

Androgenetic alopecia (AGA) is the most common progressive form of hair loss, occurring in more than half of men aged > 50 years. Hair follicle (HF) miniaturization is a feature of AGA, and dermal papillae (DP) play key roles in hair growth and regeneration by regulating follicular cell activity. Previous studies have revealed that adhesion signals are important factors in AGA development. Zyxin (ZYX) is an actin-interacting protein that is essential for cell adhesion and migration. The aim of this research was to investigate the expression and potential role of ZYX in AGA. Real-time polymerase chain reaction (RT-PCR) analysis revealed that ZYX expression was elevated in the affected frontal HF of individuals with AGA compared to unaffected occipital HF. Moreover, increased ZYX expression was also observed within DP using immunofluorescence staining. Our in vivo results revealed that ZYX knockout mice showed enhanced hair growth and anagen entry compared to wild-type mice. Reducing ZYX expression in ex vivo cultured HFs by siRNA resulted in the enhanced hair shaft production, delayed hair follicle catagen entry, increased the proliferation of dermal papilla cells (DPCs), and upregulated expression of stem cell-related proteins. These results were further validated in cultured DPCs in vitro. To further reveal the mechanism by which ZYX contributes to AGA, RNA-seq analysis was conducted to identify gene signatures upon ZYX siRNA treatment in cultured hair follicles. Multiple pathways, including focal adhesion and HIF-1 signaling pathways, were found to be involved. Collectively, we discovered the elevated expression of ZYX in the affected frontal hair follicles of AGA patients and revealed the effects of ZYX downregulation on in vivo mice, ex vivo hair follicles, and in vitro DPC. These findings suggest that ZYX plays important roles in the pathogenesis of AGA and stem cell properties of DPC and may potentially be used as a therapeutic target in AGA.

THE DRUNKEN HAIR: INTRODUCING IN VIVO DEMONSTRATION OF INCREASED BLOOD ALCOHOL CONCENTRATION TEMPORARY DISRUPTING HUMAN HAIR FOLLICLES EMISSION OF ELECTROMAGNETIC RADIATION

2020 ◽  
Vol 8 (10) ◽  
pp. 123-130
Author(s):  
Abraham A. Embi
Keyword(s):  
Electromagnetic Radiation ◽  
Hair Follicle ◽  
Human Hair ◽  
Blood Alcohol Concentration ◽  
Physical Symptoms ◽  
Alcohol Concentration ◽  
Hair Follicles ◽  
Blood Alcohol

The human hair consists of a follicle a.k.a root penetrating the skin and an outer skin structure commonly called the shaft. The hair follicle has been classified as a miniorgan having its own cells divisions; aging stages and also demonstrated to be an energy emitter in the form of electromagnetic radiation. The intent of this manuscript is to introduce documentation from in vivo experiments showing the deleterious effect of alcohol consumption on the previously documented hair follicle intrinsic and orderly emission of energy a.k.a. Electromagnetic Radiation (EMR). This was possible by a minor modification of a tabletop optical microscopy technique introduced in 2015 and designed to display plant and animals tissue EMR. In vitro control experiments had shown that a drop of white wine covering a human hair follicle placed on a glass slide caused what appeared to be a disruption on the hair follicle EMR emissions; the addition of chemicals to the wine during manufacturing could have caused that effect. The answer could lie in an in vivo alcohol drinking approach by increasing only the blood alcohol concentration (BAC). In this manuscript two in vitro and two in vivo are presented where the author, a non-alcohol drinker, purposely and during fasting underwent two binge-drinking episodes aimed to increase his BAC and investigate its impact on hair follicles. Several black beard hair samples were plucked via tweezers as controls; additional samples were also plucked and processed at approximately peak alcohol physical symptoms such cheek numbness and dizziness which occurred between 35 and 45 minutes post two episodes of wine or wine and beer binges. Images and video-recordings are presented.

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