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1.

001-es BibID:BIBFORM016014
Első szerző:Bodó Enikő
Cím:Thyroid-Stimulating Hormone, a Novel, Locally Produced Modulator of Human Epidermal Functions, Is Regulated by Thyrotropin-Releasing Hormone and Thyroid Hormones / Bodo, E., Kany, B., Gaspar, E., Knuver, J., Kromminga, A., Ramot, Y., Biro, T., Tiede, S., van Beek, N., Poeggeler, B., Meyer, K. C., Wenzel, B. E., Paus, R.
Dátum:2010
ISSN:0013-7227
Megjegyzések:Several elements of the hypothalamic-pituitary-thyroid axis (HPT) reportedly are transcribed by human skin cell populations, and human hair follicles express functional receptors for TSH. Therefore, we asked whether the epidermis of normal human skin is yet another extrathyroidal target of TSH and whether epidermis even produces TSH. If so, we wanted to clarify whether intraepidermal TSH expression is regulated by TRH and/or thyroid hormones and whether TSH alters selected functions of normal human epidermis in situ. TSH and TSH receptor (TSH-R) expression were analyzed in the epidermis of normal human scalp skin by immunohistochemistry and PCR. In addition, full-thickness scalp skin was organ cultured and treated with TSH, TRH, or thyroid hormones, and the effect of TSH treatment on the expression of selected genes was measured by quantitative PCR and/or quantitative immunohistochemistry. Here we show that normal human epidermis expresses TSH at the mRNA and protein levels in situ and transcribes TSH-R. It also contains thyrostimulin transcripts. Intraepidermal TSH immunoreactivity is up-regulated by TRH and down-regulated by thyroid hormones. Although TSH-R immunoreactivity in situ could not be documented within the epidermis, but in the immediately adjacent dermis, TSH treatment of organ-cultured human skin strongly up-regulated epidermal expression of involucrin, loricrin, and keratins 5 and 14. Thus, normal human epidermis in situ is both an extrapituitary source and (possibly an indirect) target of TSH signaling, which regulates defined epidermal parameters. Intraepidermal TSH expression appears to be regulated by the classical endocrine controls that determine the systemic HPT axis.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:Endocrinology. - 151 : 4 (2010), p. 1633-1642. -
További szerzők:Kany Benedikt Gáspár Erzsébet Knüver, Jana Kromminga, Arno Ramot, Yuval Bíró Tamás (1968-) (élettanász) Tiede, Stephan van Beek, Nina Poeggeler, Burkhard Meyer, Katja C. Wenzel, Björn E. Paus, Ralf
Internet cím:DOI
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2.

001-es BibID:BIBFORM048963
Első szerző:Ernst, Nancy
Cím:β1 integrin signaling maintains human epithelial progenitor cell survival in situ and controls proliferation, apoptosis and migration of their progeny / Nancy Ernst, Arzu Yay, Tamás Bíró, Stephan Tiede, Martin Humphries, Ralf Paus, Jennifer E. Kloepper
Dátum:2013
ISSN:1932-6203
Megjegyzések:β1 integrin regulates multiple epithelial cell functions by connecting cells with theextracellular matrix (ECM). While β1 integrin-mediated signaling in murine epithelialstem cells is well-studied, its role in human adult epithelial progenitor cells (ePCs) insitu remains to be defined. Using microdissected, organ-cultured human scalp hairfollicles (HFs) as a clinically relevant model for studying human ePCs within theirnatural topobiological habitat, β1 integrin-mediated signaling in ePC biology wasexplored by β1 integrin siRNA silencing, specific β1 integrin-binding antibodies andpharmacological inhibition of integrin-linked kinase (ILK), a key component of theintegrin-induced signaling cascade. β1 integrin knock down reduced keratin 15expression as well as the proliferation of outer root sheath keratinocytes (ORSKs).Embedding of HF epithelium into an ECM rich in β1 integrin ligands that mimic the HFmesenchyme significantly enhanced proliferation and migration of ORSKs, while K15and CD200 gene and protein expression were inhibited. Employing ECM-embedded?1 integrin-activating or -inhibiting antibodies allowed to identify functionally distincthuman ePC subpopulations in different compartments of the HF epithelium. The β1integrin-inhibitory antibody reduced β1 integrin expression in situ and selectivelyenhanced proliferation of bulge ePCs, while the ?1 integrin-stimulating antibodydecreased hair matrix keratinocyte apoptosis and enhanced transferrin receptor(CD71) immunoreactivity, a marker of transit amplifying cells, but did not affect bulgeePC proliferation. That the putative ILK inhibitor QLT0267 significantly reduced ORSKmigration and proliferation and induced massive ORSK apoptosis suggests a key rolefor ILK in mediating the β1 integrin effects. Taken together, these findings demonstratethat ePCs in human HFs require 1 integrin-mediated signaling for survival, adhesion,and migration, and that different human HF ePC subpopulations differ in their responseto β1 integrin signaling. These new insights inform cell-based regenerative medicinestrategies that employ human HF-derived ePCs.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Hair follicle
1 integrin
epithelial progenitor cells
extracellular matrix
Signaling
Megjelenés:Plos One. - 8 : 12 (2013), p. e84356. -
További szerzők:Yay, Arzu Bíró Tamás (1968-) (élettanász) Tiede, Stephan Humphries, Martin J. Paus, Ralf Kloepper, Jennifer E.
Internet cím:Intézményi repozitóriumban (DEA) tárolt változat
DOI
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3.

001-es BibID:BIBFORM039252
Első szerző:Gáspár Erzsébet
Cím:Thyrotropin-Releasing Hormone Selectively Stimulates Human Hair Follicle Pigmentation / Gáspár, Erzsébet, Nguyen-Thi, Kim T, Hardenbicker Celine, Tiede Stephan, Plate Christian, Bodó Enikő, Knuever Jana, Funk Wolfgang, Bíró Tamás, Paus Ralf
Dátum:2011
ISSN:0022-202X
Megjegyzések:In amphibians, thyrotropin-releasing hormone (TRH) stimulates skin melanophores by inducing secretion of α-melanocyte-stimulating hormone in the pituitary gland. However, it is unknown whether this tripeptide neurohormone exerts any direct effects on pigment cells, namely, on human melanocytes, under physiological conditions. Therefore, we have investigated whether TRH stimulates pigment production in organ-cultured human hair follicles (HFs), the epithelium of which expresses both TRH and its receptor, and/or in full-thickness human skin in situ. TRH stimulated melanin synthesis, tyrosinase transcription and activity, melanosome formation, melanocyte dendricity, gp100 immunoreactivity, and microphthalmia-associated transcription factor expression in human HFs in a pituitary gland-independent manner. TRH also stimulated proliferation, gp100 expression, tyrosinase activity, and dendricity of isolated human HF melanocytes. However, intraepidermal melanogenesis was unaffected. As TRH upregulated the intrafollicular production of "pituitary" neurohormones (proopiomelanocortin transcription and ACTH immunoreactivity) and as agouti-signaling protein counteracted TRH-induced HF pigmentation, these pigmentary TRH effects may be mediated in part by locally generated melanocortins and/or by MC-1 signaling. Our study introduces TRH as a novel, potent, selective, and evolutionarily highly conserved neuroendocrine factor controlling human pigmentation in situ. This physiologically relevant and melanocyte sub-population-specific neuroendocrine control of human pigmentation deserves clinical exploration, e.g., for preventing or reversing hair graying.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:Journal Of Investigative Dermatology. - 131 : 12 (2011), p. 2368-2377. -
További szerzők:Nguyen-Thi, Kim T Hardenbicker, Celine Tiede, Stephan Plate, Christian Bodó Enikő Knüver, Jana Funk, Wolfgang Bíró Tamás (1968-) (élettanász) Paus, Ralf
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DOI
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4.

001-es BibID:BIBFORM020307
035-os BibID:WOS:000293282700039
Első szerző:Ramot, Yuval
Cím:Spermidine promotes human hair growth and is a novel modulator of human epithelial stem cell functions / Ramot Y., Tiede S., Biro T., Abu Bakar M. H., Sugawara K., Philpott M. P., Harrison W., Pietila M., Paus R.
Dátum:2011
ISSN:1932-6203
Megjegyzések:Rapidly regenerating tissues need sufficient polyamine synthesis. Since the hair follicle (HF) is a highly proliferative mini-organ, polyamines may also be important for normal hair growth. However, the role of polyamines in human HF biology and their effect on HF epithelial stem cells in situ remains largely unknown. Methods and Findings: We have studied the effects of the prototypic polyamine, spermidine (0.1-1 mu M), on human scalp HFs and human HF epithelial stem cells in serum-free organ culture. Under these conditions, spermidine promoted hair shaft elongation and prolonged hair growth (anagen). Spermidine also upregulated expression of the epithelial stem cell-associated keratins K15 and K19, and dose-dependently modulated K15 promoter activity in situ and the colony forming efficiency, proliferation and K15 expression of isolated human K15-GFP+ cells in vitro. Inhibiting the rate-limiting enzyme of polyamine synthesis, ornithine decarboyxlase (ODC), downregulated intrafollicular K15 expression. In primary human epidermal keratinocytes, spermidine slightly promoted entry into the S/G2-M phases of the cell cycle. By microarray analysis of human HF mRNA extracts, spermidine upregulated several key target genes implicated e.g. in the control of cell adherence and migration (POP3), or endoplasmic reticulum and mitochondrial functions (SYVN1, NACA and SLC25A3). Excess spermidine may restrict further intrafollicular polyamine synthesis by inhibiting ODC gene and protein expression in the HF's companion layer in situ. Conclusions: These physiologically and clinically relevant data provide the first direct evidence that spermidine is a potent stimulator of human hair growth and a previously unknown modulator of human epithelial stem cell biology.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:PLoS One. - 6 : 7 (2011), p. e22564. -
További szerzők:Tiede, Stephan Bíró Tamás (1968-) (élettanász) Abu Bakar, Mohd Hilmi Sugawara, Koji Philpott, Michael P. Harrison, Wesley Pietila, Marko Paus, Ralf
Internet cím:DOI
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5.

001-es BibID:BIBFORM014368
Első szerző:Ramot, Yuval
Cím:Prolactin - a novel neuroendocrine regulator of human keratin expression in situ / Yuval Ramot, Tamás Bíró, Stephan Tiede, Balázs I. Tóth, Ewan A. Langan, Koji Sugawara, Kerstin Foitzik, Arieh Ingber, Vincent Goffin, Lutz Langbein, Ralf Paus
Dátum:2010
ISSN:0892-6638
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Megjelenés:The FASEB Journal. - 24 : 6 (2010), p. 1768-1779. -
További szerzők:Bíró Tamás (1968-) (élettanász) Tiede, Stephan Tóth István Balázs (1978-) (élettanász) Langan, Ewan A. Sugawara, Koji Foitzik, Kerstin Ingber, Arieh Goffin, Vincent Langbein, Lutz Paus, Ralf
Internet cím:Szerző által megadott URL
DOI
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