Hair Follicle Tissue Research Articles

Mommy — where do tumors come from?

Identification of the cell of origin of cancers is a hot topic, and recently no fewer than five groups have addressed this question for basal cell carcinomas (BCCs) of the skin. In this issue of the JCI, Grachtchouk et al. present evidence from engineered mouse models that at least some BCCs can arise from hair follicle tissue stem cells. Although these cells sustain oncogenic mutations while in the stem cell niche, they may have to leave that stem cell niche to become tumor cells.

Induction of synapse associated protein 102 expression in cyclosporin A‐stimulated hair growth

Cyclosporin A (CsA) has been used as a potent immunosuppressive agent for inhibiting the graft rejection after organ transplantation. However, CsA provokes lots of side effects including hirsutism, the phenomenon of abnormal hair growth in the body. In the present study, we investigated the hair growth stimulating effect of CsA using in vivo and in vitro test models. When topically applied on the back skin of mice, CsA induced fast telogen to anagen transition. In contrast, CsA had no effect on the growth of human hair follicle tissues cultured in vitro, indicating that it might not have the mitogenic effect on hair follicles. To identify the genes related with CsA-induced hair growth, we performed differential display RT-PCR. Among the genes obtained, the expression of synapse associated protein 102 (SAP102) was verified using competitive RT-PCR. The result showed that the expression of SAP102 was significantly induced by CsA treatment in the back skin of C57BL/6 mice. However, the increase of SAP102 mRNA was also seen in spontaneous anagen mice, suggesting that induction of SAP102 is one event of the anagen hair growth response regardless of how the growth state was induced. SAP102 was not expressed in cultured human hair outer root sheath and dermal papilla cells. Immunohistochemistry analysis showed that CsA induced the expression of SAP102 in perifollicular region of mouse anagen hair. Together, these results suggest that SAP102 is one of hair-cycle-dependent genes, whose expression is related with the anagen progression.

Promoted Growth of Murine Hair Follicles by Controlled Release of Growth Factors from Biodegradable Hydrogel

This study is an investigation to evaluate how the controlled release of different growth factors affects the hair follicle growth of mice in the second anagen stage of hair cycle. For the controlled release of basic fibroblast growth factor (bFGF) and hepatocyte growth factor (HGF), they were incorporating into biodegradable gelatin hydrogels, while a biodegradable collagen hydrogel was used for incorporation of vascular endothelial growth factor (VEGF). After subcutaneous implantation of the different hydrogels incorporating each growth factor or injection of phosphate buffered saline (PBS) containing the same dose of growth factor into the back of mice, the hair follicle growth was evaluated photometrically and histologically based on four parameters: the skin color of reverse side of the implanted or injected site, the number of vessels newly formed, the area occupied by hair follicle tissue, and the hair length. The area in close proximity to the implanted site of hydrogels incorporating growth factor was still dark in color 10 days after application. The hydrogel incorporating any type of growth factor enabled the hair follicles to increase the size, leading significantly enhanced area occupied by hair follicles per unit area of tissue. Implantation of the hydrogels incorporating growth factor increased significantly the number of blood vessels newly formed. Moreover, the length of hair shaft was elongated by the hydrogel incorporating growth factor to a significantly higher extent than the corresponding growth factor. Neither empty gelatin nor collagen hydrogels affected the hair follicle growth. These results indicate that the hydrogel incorporating growth factor induced the anagen-preservable activity. We conclude that the controlled release enabled growth factors to positively act on the hair growth cycle of mice, irrespective of the factor type.

Promoted growth of murine hair follicles through controlled release of basic fibroblast growth factor.

This study is an investigation to evaluate how the controlled release of basic fibroblast growth factor (bFGF) affects the hair follicle growth of mice in different hair cycle stages: second anagen and second telogen. bFGF was incorporated into biodegradable gelatin hydrogels for its controlled release. After subcutaneous implantation of gelatin hydrogels incorporating 0, 0.7, 7, and 70 microg of bFGF or injection of 0 and 70 microg of free bFGF into the backs of mice, hair follicle growth was evaluated photometrically and histologically on the basis of three parameters: skin color of the reverse side of the implanted or injected site, skin thickness, and area occupied by hair follicle tissue. For mice in second anagen, the darkness of the reverse side of skin implanted with gelatin hydrogel incorporating 7 microg of bFGF was significantly higher than that of skin injected with 70 microg of bFGF 10 days after bFGF application. Implantation of gelatin hydrogel incorporating bFGF enabled the hair follicles to increase the area occupied in skin tissue to a significantly greater extent than in other groups, whereas no effect on skin thickness was observed. bFGF-free, empty gelatin hydrogels did not affect hair follicle growth. Moreover, hair shaft length was significantly elongated by gelatin hydrogel incorporating 7 microg of bFGF, in marked contrast to other agents. The skin of telogen mice receiving gelatin hydrogel incorporating 7 microg of bFGF did not show any change in darkness of reverse skin side or skin thickness, but a significant increase in the size of hair follicles 10 days later. These results indicate that the controlled release of bFGF positively affects the hair growth cycle of mice.

Dissection of promoter control modules that direct Bmp4 expression in the epithelium-derived components of hair follicles

Bone morphogenetic protein 4 (Bmp4) plays a significant role in development. Using transgenic approaches, we studied the mechanisms controlling Bmp4 expression during primordial and mature tissue development, as well as in epithelium- and mesenchyme-derived components with hair follicles as a model. In this report, we demonstrated that the promoter region between the −0.26 and the −1.14 kb, highly conserved between human and mouse, controls Bmp4 expression in the epithelium-derived tissues but not in mesenchyme-derived tissues of hair follicles, suggesting that control modules for Bmp4 expression in epithelium-derived tissues and mesenchyme originated tissues are in separate regions. Using live embryos and mice, we demonstrated the temporal and spatial activities of these modules. We also demonstrated that control regions for Bmp4 expression in primordial and differentiated hair follicle tissues are separated. Therefore we present a model to explain a mechanism controlling expression of the Bmp4 gene in different tissue types, as well as different development stages as related to hair development.

Promoted growth of murine hair follicles through controlled release of vascular endothelial growth factor

The objective of this study is to investigate whether or not the controlled release of vascular endothelial growth factor (VEGF) is effective in promoting the hair follicle growth of mice in second anagen of hair cycle. VEGF was incorporated into a biodegradable collagen hydrogel for its controlled release. Following implantation of the collagen hydrogel incorporating 0 or 2 μg of VEGF and injection of 0 or 2 μg of VEGF in the solution form into the back subcutis of mice, the hair follicle growth was evaluated photometrically and histologically in terms of the skin color of reverse side of the implanted or injected site, the skin thickness, and the area occupied by hair follicle tissue. Ten days later, the skin color of mice implanted with the collagen hydrogel incorporating 2 μg of VEGF was significantly darker than that injected with 2 μg of VEGF. The collagen hydrogel incorporating VEGF increased the hair follicle area at the implanted site to a significantly greater extent than other agents while significant angiogenetic effect in the skin tissue was observed. VEGF-free, empty collagen hydrogels did not affect the skin darkness, hair follicle growth, and the angiogenesis. Moreover, the hair shaft length was significantly elongated by the collagen hydrogel incorporating VEGF, in marked contrast to other agents. Immunohistolchemicalstaining with proliferating cell nuclear antigen revealed that the collagen hydrogel incorporating VEGF promoted the proliferation of cells around the hair follicle more frequently than free VEGF. We concluded that the controlled release of VEGF more positively acted on the hair growth cycle of mice for hair growth than the injection of free VEGF.

Protein and sulphur amino acid nutrition of hair fibre-producing Angora and Cashmere goats

The results from a number of studies are presented which investigated responses in fibre production of British Cashmere and Angora goats to variation in protein and sulphur amino acid nutrition under conditions of active fibre growth. Requirements for amino acids were considered in the context of the concentration of amino acids, including cysteine and methionine, in rumen microbial protein and in dietary protein supplements compared with the amino acid composition of hair fibre. Increases in fibre yield and diameter were consistently observed in Angora goats given good quality protein supplements or rumen-protected intestinally-available methionine (Smartamine™M, Rhône-Poulenc). Cashmere yield was not influenced by urea or white fishmeal supplementation but responded positively (in contrast to other studies in the literature) to additional dietary methionine. While responses in cashmere production have been recorded in response to protein supplementation at sub-maintenance levels of nutrition, it is suggested that one component of the absent or reduced response at above maintenance may be the smaller quantitative synthesis of this fibre compared with mohair production by Angora goats. The results are considered in the context of studies from the sheep literature in which protein and amino acid supplementation were shown to stimulate proliferation of hair forming cells in the wool follicle and to increase deposition of protein fractions containing high concentrations of sulphur-containing amino acids. Results from an in vitro study suggested that methionine could support cashmere fibre growth (approximately 0.75) in the absence of cysteine and cystine, providing evidence that methionine is essential for fibre production and that transulphuration occurs in isolated hair follicles. However, cysteine and cystine were also required to produce maximum growth. In the context of competition between the hair follicle and other body tissues, data are presented which illustrate the increases in nitrogen retention and/or anabolic growth response to protein or protected-methionine supplementation in non-integumental tissues of Cashmere and Angora goats also, despite the presence of lower concentrations of sulphur-containing amino acids in these tissues. The results confirm the value of a good quality protein supplement or more targeted supply of rumen-protected intestinally-available methionine to correct a frequently apparent deficiency in sulphur amino acid supply for (a) growth of hair fibre by Angora goats and, less consistently, by Cashmere goats and (b) other body tissues in both genotypes.

Gene Expression of Mouse S100A3, a Cysteine-Rich Calcium-Binding Protein, in Developing Hair Follicle

We have previously identified a cysteine-rich calcium binding protein S100A3 present in the cuticle of human hair fiber. In this study, we cloned a cDNA for mouse S100A3, identified its gene location, and elucidated the expression profile throughout hair follicle development. The mouse S100A3 gene was clustered with other S100 family members on chromosome 3, and specifically expressed in dorsal skin containing hair follicles. The level of S100A3 mRNA was elevated during the anagen phase of the hair growth cycle, and sharply declined from the regression phase on. In situ hybridization revealed that the S100A3 gene was prominently expressed in cuticular cells of the hair follicle, and mRNA levels were highest in the keratogenous zone over the entire cuticular layer. Expression was also observed to a lesser extent in differentiated cortical cells; however, expression was not observed in any other component of the hair follicle or dorsal tissues. Immunohistochemical analysis showed that the S100A3 protein accumulated in cuticular and cortical cells undergoing terminal differentiation. These results indicate that the S100A3 gene is exclusively expressed, and the translation product retained, in follicular cells differentiating into major components of the hair shaft. It seems likely that S100A3 plays an important role in calcium-dependent processes leading to hair shaft formation.

Local Injection of Hepatocyte Growth Factor/Scatter Factor (HGF/SF) Alters Cyclic Growth of Murine Hair Follicles

Hepatocyte growth factor/scatter factor (HGF/SF) has recently been shown to stimulate the hair follicle growth of mouse vibrissae in vitro. In this study, we analyzed the effect of cutaneous injections of recombinant human HGF/SF on hair follicle growth using mice in different hair cycle stages. Five male newborn mice, five male mice in second anagen, and five male mice in second telogen were administered a dorsal intradermal injection of 1 microg HGF/SF dissolved in 0.1% albumin-phosphate-buffered saline once daily for five or seven consecutive days, and then sacrificed on days 7 or 10. Hair follicle growth was evaluated photometrically and histologically using three parameters: the skin color of the reverse side of the resected skin, the skin thickness, and the area occupied by hair follicle tissue. The HGF/SF injected skin of newborn mice had hair follicles that were histologically longer and larger than those of the 0.1% albumin-phosphate-buffered saline injected skin. Mice that had received HGF/SF injection in second anagen, retained anagen hair follicles after 10 d only at the injection site, suggesting that HGF/SF delayed the transition from anagen to telogen. The HGF/SF injected skin of telogen mice had a significant increase in hair follicle tissue in the dermis, suggesting a mild anagen inducible activity by HGF/SF. Furthermore, precise measurements of the 20 hairs plucked from the HGF/SF injection sites revealed mild hair elongation in all the aforementioned experiments. These results imply that HGF/SF acts as a paracrine factor that alters cyclic hair growth of mice.

Radiation Sensitivity of Human Hair Follicles in SCID-hu Mice

We developed an experimental model for studying the growth and epilation of the human hair follicle by implanting human scalp tissue onto immunodeficient C.B-17 scid/scid mice. The skin grafts showed continuous growth of black human hairs for at least 1 year and maintained the normal histological structure of a human hair follicle and other tissues associated with the skin. Using this in vivo model, we evaluated the effect of irradiation on the function of human hair follicles. Localized X irradiation (1 to 6 Gy) induced hair loss dose-dependently and synchronously in the third week after irradiation. The hairs undergoing epilation showed a gradual decrease in width toward the root. The minimum width at the thinnest portion of the surviving hair 4 weeks after irradiation suggested that epilation resulted from the breaking of hairs when the hair width decreased to less than 20 microm. After the highest-dose irradiation, the normal structure of the hair bulb was totally abrogated, and long and narrow epithelial tissues associated with regressed papillary cells remained. The surviving epithelia were morphologically similar to the outer epithelial sheath of the follicle associated with palisadic basal cell layers. In the third week some cells in the basal layers of the surviving epithelium in each follicle expressed proliferating cell nuclear antigen. By about 9 weeks after irradiation, the complete structure of the follicle regenerated, with hair growth activity even in the grafts irradiated at the highest dose, although about 30% of the hairs did not regrow. These findings suggest that follicular stem cells that survive high-dose exposure in the sheath-like epithelial tissue can reproduce the complete follicle structure. This animal model can be used to assess the effects of radiation exposure on human skin and to identify and characterize human follicular stem cells.

Transcripts for two members of the transforming growth factor-beta superfamily BMP-3 and BMP-7 are expressed in developing rat embryos.

Bone morphogenetic protein-3 (BMP-3) and BMP-7 are members of the transforming growth factor beta superfamily that have been implicated in the formation of cartilage and bone. Using in situ hybridization, we localized mRNAs for BMP-3 and BMP-7 during organogenesis in rats. Both mRNAs were expressed in a variety of cells, in particular, in the developing hair follicle, tooth, kidney, and lung tissues, in which reciprocal epithelial-mesenchymal interactions are essential. In some tissues, the distribution of BMP-3 and BMP-7 mRNAs overlapped. In other tissues, the patterns of expression were quite different. Moreover, the site of expression of the transcripts changed from one cell type to another during organogenesis. These results suggest that BMP-3 and BMP-7 play important roles in organogenesis and that the differential patterns of their expression might reflect their distinct roles in embryogenesis.

Hair follicle-like change over histiocytomas.

Epidermal hyperplasia is a common finding overlying histiocytomas. Occasionally, a distinctive type of basaloid hyperplasia occurs, with differentiation into primitive hair follicle tissue. This study attempts to characterize this change and determine whether it is associated with any particular clinical or histological feature. Data from patients with histiocytomas displaying induction of pilar epithelium in the epidermis above the lesions was compared with data from controls who did not show this change. The size, site, and duration of histiocytomas were similar in both groups, as were the predominant cell type and distance of histiocytoma from the epidermis. Serial sectioning of histiocytomas showed that the induction of pilar epithelium was a focal phenomenon, often missed in routine sections. It is suggested that histiocytoma cells may produce a "hair organizing mediator."

Characterization of the proteins of guinea-pig hair and hair-follicle tissue.

This work forms a part of a study of the mechanism and control of protein synthesis in the hair follicle and concerns the characterization of the proteins of hair-follicle tissue and for comparative reasons those of the hair itself. 1. Five different groups of reduced carboxymethylated proteins were delineated from both tissues; these were: group 1A proteins, which appeared to be aggregates of the group 2 proteins; group 1B proteins, soluble at pH4.4, which were thought to originate from the medulla and inner-rootsheath layers; group 2 proteins, which were defined as the main low-sulphur keratin proteins insoluble at pH4.4; group 3 proteins, the precise origin of which is not known; and the group 4 proteins, which were defined as the main high-sulphur keratin proteins soluble at pH4.4. 2. With the single exception of the group 1B proteins, the types and properties of all hair and hair-follicle proteins were identical as far as could be determined by use of such criteria as multiplicity of components, molecular charge, molecular weight and amino acid composition. 3. Two significant quantitative differences were noted: in follicle extracts there were more group 2 proteins but less group 3 and group 4 proteins than in hair extracts; and secondly, in the follicle group 4 proteins, there were more proteins of lowest molecular weight and S-carboxymethylcysteine content, but fewer proteins of the highest molecular weight and S-carboxymethylcysteine conent than in the hair group 4 proteins. 4. These quantitative differences are discussed in terms of the mechanism of synthesis of the keratin proteins. 5. Follicle group 1B proteins are postulated to have arisen from the trichohyalin droplets of the developing medulla and inner-root-sheath layers of the follicle and may be precursors of the proteins of the mature medulla and inner root sheath.

In vitro studies on the synthesis of guinea pig hair keratin proteins

1. The “high-sulphur” keratin proteins that comprise the matrix moiety of hair have been synthesized in a cell-free protein synthesis system from guinea pig hair follicle tissue. 2. These findings, in conjunction with the previous studies on the cell-free synthesis of the “low-sulphur” keratin proteins, demonstrate that the keratin proteins are synthesized in vivo by the classical ribosomal-dependent mechanism. This conclusion makes unlikely the suggestions by other workers that a non-ribosomal-dependent mechanism could be responsible for the basic synthesis of the keratin proteins. 3. Estimates were made of the amount of de novo synthesis of the low-sulphur proteins and the high-sulphur proteins. It was found that 14–18 % of all low-sulphur proteins synthesised in vitro were synthesised de novo and only about 2 % for the high-sulphur proteins. It is proposed that the findings could reflect differences in the rates of translation of the mRNAs for the low-sulphur and high-sulphur proteins. Since these proteins contain high and variable amounts of S- carboxymethylcysteine , then the level of cysteinyl-tRNA may limit the rates of translation in vitro. This conclusion is discussed in relation to observations on the synthesis of the keratin proteins in vivo.

The mineralization of hair follicle tissue. II. An in vitro study.

The mineralization of hair follicle tissue. II. An in vitro study.

The mineralization of hair follicle tissue. I. An in vivo study.

Previous histological investigations have shown that the hair follicle is particularly susceptible to mineralization when the skin of hypercalcaemic rats is injured. Direct chemical and X-ray diffraction analyses of follicle tissue have now confirmed this finding. As judged by increases in both calcium and phosphorus, mineral deposits began to form in hair follicle tissue 6–12 h after a mild crush injury to the skin of rats dosed with dihydrotachysterol (DHT), and 24–48 h after a similar injury to the skin of non-dosed rats. X-ray diffraction gave a diffuse apatite pattern. Within 3 h of injury there was a rise in the calcium content of follicle tissue which was not related to DHT-dosing and which was probably a reflection of calcium binding rather than mineral deposition.

The synthesis of hair keratin proteins in vitro

The “low-sulphur” keratin proteins that comprise the major fibrous protein of hair have been synthesised in a reconstituted cell-free system containing polyribosomes and supernatant factors isolated from guinea pig hair follicle tissue. The evidence for this is precise co-chromatography on Sephadex and co-electrophoresis on acrylamide gels of the radioactively labelled proteins synthesised in vitro with the native proteins extracted from the hair follicle. Further evidence is that the labelled proteins precipitated with antisera prepared against the native hair follicle “low-sulphur” keratin proteins.

Protein biosynthesis in cell-free systems prepared from hair follicle tissue of guinea pigs

1. Polyribosomes have been prepared from the hair follicle tissue of young albino guinea pigs and the yields of especially the larger polyribosomes greatly exceeded those isolated from the same source in earlier studies. 2. These polyribosomes were also highly active in cell-free protein synthesis, being about 700 times more active than those prepared previously. 3. The ribonuclease content of the tissue homogenate preparations from young animals was found to be markedly lower than that obtained from older animals and it was concluded that this lower ribonuclease content was responsible for the improved findings in this work. 4. The properties of the protein synthesis systems established from the guinea pig hair follicle polyribosomes have been investigated using standard techniques. During amino acid incorporation, the polyribosomes degraded by an orderly process of run-off of ribosomes from the mRNA followed by release of the nascent protein chains. Experiments suggested that considerable reinitiation of protein chains occurred during incubation. These and other properties of the cell-free protein synthesis systems are similar to those of other animal systems and thus it is concluded that they are typically of the eukaryote cell-type.

Protein Synthesis in the Hair Follicle. II. Polysomes and Amino Acid Incorporation

Single ribosomes and polysomes were isolated from guinea pig hair follicle tissue by sucrose density gradient centrifugation and characterized by electron microscopy. Single ribosomes are held together by ribonucleic acid to form polysomes in the follicle cell as indicated by the disaggregating effect of added ribonuclease. Furthermore, the ribosomal population incorporates labeled amino acids into protein and requires those factors necessary for protein synthesis in other systems. The effects of added inhibitors of protein synthesis as well as artificial mRNA on the incorporation activity of hair follicle tissue are discussed in respect to our present knowledge of keratin synthesis.