Cell kinetic study of human and mouse hair tissues using anti-bromodeoxyuridine monoclonal antibody

Tezuka, Masaya; Ito, Masaaki; Ito, Kei; Satō, Yoshio

doi:10.1016/0923-1811(90)90590-a

Cited by 19 publications

(8 citation statements)

References 17 publications

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“…However, treatment with an excessive dose of BrdUrd leads to cell damage, especially in highly proliferative cells. Here we treated mice with BrdUrd at doses about 10 times higher than routinely used for labeling in vivo (14). When BrdUrd was used for pulsed labeling on PND 10-11, which is around the late anagen of the first hair cycle, it was rapidly incorporated in the highly proliferative cells in the bulb, i.e., hair matrix cells (data not shown).…”

Section: Stat3 Ablation In Keratinocytes Results In Impairment Of Thementioning

confidence: 99%

“…To verify the impairment of hair growth in the second anagen, we shed the first anagen-derived hair by pulsing with BrdUrd. BrdUrd is an analogue of thymidine and is incorporated in cells synthesizing DNA, so it is widely used to detect proliferating cells with anti-BrdUrd antibody (14). However, treatment with an excessive dose of BrdUrd leads to cell damage, especially in highly proliferative cells.…”

Section: Stat3 Ablation In Keratinocytes Results In Impairment Of Thementioning

confidence: 99%

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Two distinct signaling pathways in hair cycle induction: Stat3-dependent and -independent pathways

Sano

Kira

Takagi

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

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The hair follicle is an epidermal derivative that undergoes cycles of growth, involution, and rest. The hair cycle has well-orchestrated kinetics regulated by interactions between mesenchymal and epithelial cells, although the intracellular signals remain unclear. We previously established keratinocyte-specific Stat3-disrupted mice, by which we demonstrated that signal transducer and activator of transcription 3 (Stat3) is required for wound healing and anagen progression in the hair cycle. Growth factor-dependent migration of Stat3-disrupted keratinocytes was severely impaired, suggesting that not only wound healing but also telogen-to-anagen progression required organized keratinocyte migration in response to mesenchymal stimuli. In the present study, to examine whether Stat3 activation in keratinocytes is a prerequisite for hair cycle progression, we applied methods for experimental anagen induction to Stat3-disrupted mice. It was demonstrated that anagen was successfully induced in Stat3-disrupted as well as wild-type mice by chemical or mechanical stimulation, i.e., by topical application of phorbol 12-myristate 13-acetate (PMA) or by hair plucking, respectively. This result indicated that anagen in these methods occurred in the absence of Stat3. Furthermore, PMA stimulated the migration of Stat3-disrupted keratinocytes in vitro , supporting a hypothesis that the protein kinase C (PKC) and Stat3 pathways occur independently in the postnatal anagen induction. Both Stat3-dependent and -independent migration of keratinocytes was inhibited by a phosphoinositide 3-kinase (PI3K) inhibitor, wortmannin. Therefore, we infer that entry into anagen is mediated by at least two distinct signaling pathways: Stat3-dependent pathway for spontaneous hair cycling and Stat3-independent (probably PKC-dependent) pathway for exogenously induced hair cycling, whereas both pathways require PI3K activation.

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Section: Stat3 Ablation In Keratinocytes Results In Impairment Of Thementioning

confidence: 99%

Section: Stat3 Ablation In Keratinocytes Results In Impairment Of Thementioning

confidence: 99%

Two distinct signaling pathways in hair cycle induction: Stat3-dependent and -independent pathways

Sano

Kira

Takagi

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

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“…A similar role is evident for the epidermal compartments of the skin, i.e., epidermis and hair follicle. For instance, withdrawal of IGF-I from the medium of cultured hair follicles induced a transformation reminiscent of the regression phase of the hair cycle which is characterised by a stop of proliferation in the epithelial compartment (Philpott et al, 1994;Tezuka et al, 1990). On the other hand, transgenic expression of Igf-I in the interfollicular epidermis causes epidermal hyperplasia, whereas ectopic expression in the hair follicle stimulates vibrissa growth and an increase in length and width of pelage hair shafts (Bol et al, 1997;Su et al, 1999;Weger and Schlake, 2005b).…”

Section: Introductionmentioning

confidence: 99%

Krox20, a novel candidate for the regulatory hierarchy that controls hair shaft bending

Schlake

2006

Mechanisms of Development

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Murine hair follicle morphogenesis gives rise to four distinct pelage follicle types that produce hair shafts differing in length, the number of medulla columns, and the presence and number of bends. Recently, Igfbp5 was identified as the first molecular marker that distinguishes among different hair follicle types and shown to mark zigzag hairs. Further, it was demonstrated that Igfbp5 expression is modulated by FGF signalling. Here, we identify Krox20 as a molecular marker whose expression in the proximal follicle appears to be restricted to zigzag hair follicles. Gene transcription occurs in precursors and early differentiating cells of the medulla. Spatial and temporal expression of Krox20 and Igfbp5 seem to be tightly co-regulated in wildtype follicles. This correlation also holds in transgenic mice in which Igfbp5 expression is disturbed. Inspection of the Igfbp5 promoter reveals several putative binding sites for KROX20. In transfection studies, KROX20 strongly stimulates transcription from a 1.5kb Igfbp5 promoter fragment which is significantly reduced by site-directed mutagenesis of putative KROX20 binding sites, indicating a potential role of KROX20 in activating Igfbp5 expression. Our data suggest Krox20 as a nodal point of FGF and IGF signalling pathways controlling Igfbp5 expression which is associated with hair shaft differentiation and may generate the periodicity of the zigzag hair.

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“…Early evidence came from in vitro cultures of human hair follicles in the growth phase. Withdrawal of IGF-I from the medium induced a transformation reminiscent of the regression phase of the hair cycle which is characterised by a stop of proliferation in the epithelial compartment (Philpott et al, 1994;Tezuka et al, 1990). On the contrary, transgenic expression of Igf-I in the interfollicular epidermis causes epidermal hyperplasia, whereas ectopic expression in the hair follicle stimulates vibrissa growth (Bol et al, 1997;Su et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

Segmental Igfbp5 expression is specifically associated with the bent structure of zigzag hairs

Schlake

2005

Mechanisms of Development

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The murine hair coat consists of four different hair types that are characterised by hair length, the number of medulla columns, and the presence and number of bends. The molecular mechanisms underlying the establishment and maintenance of distinct hair follicle fates are unknown. We identify Igfbp5 as the first molecular marker that distinguishes among different hair follicle types. High-resolution expression analysis revealed that its expression in the medulla of hair shafts is associated with the bend-forming zones of zigzag hairs. To directly examine the functional importance of segmental gene expression in the hair follicle, we have generated transgenic mice expressing Igfbp5 in differentiating keratinocytes of the medulla and inner root sheath. Ectopic expression of Igfbp5 resulted in the appearance of remarkable curvatures and thinning of hair shafts, two hallmarks of hair bends. Both effects and the natural bending process are under negative control of IGF signalling. Thus, our data identify Igfbp5 as a central regulator of hair shaft differentiation and hair type determination.

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Cell kinetic study of human and mouse hair tissues using anti-bromodeoxyuridine monoclonal antibody

Cited by 19 publications

References 17 publications

Two distinct signaling pathways in hair cycle induction: Stat3-dependent and -independent pathways

Two distinct signaling pathways in hair cycle induction: Stat3-dependent and -independent pathways

Krox20, a novel candidate for the regulatory hierarchy that controls hair shaft bending

Segmental Igfbp5 expression is specifically associated with the bent structure of zigzag hairs

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