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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
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2.

001-es BibID:BIBFORM048815
Első szerző:Langan, Ewan A.
Cím:Tumour necrosis factor alpha, interferon gamma and substance P are novel modulators of extrapituitary prolactin expression in human skin / Ewan A. Langan, Silvia Vidali, Natascha Pigat, Wolfgang Funk, Erika Lisztes, Tamás Bíró, Vincent Goffin, Christopher E. M. Griffiths, Ralf Paus
Dátum:2013
ISSN:1932-6203
Megjegyzések:Human scalp skin and hair follicles (HFs) are extra-pituitary sources of prolactin (PRL). However, the intracutaneous regulation of PRL remains poorly understood. Therefore we investigated whether well-recognized regulators of pituitary PRL expression, which also impact on human skin physiology and pathology, regulate expression of PRL and its receptor (PRLR) in situ. This was studied in serum-free organ cultures of microdissected human scalp HFs and skin, i.e. excluding pituitary, neural and vascular inputs. Prolactin expression was confirmed at the gene and protein level in human truncal skin, where its expression significantly increased (p?=?0.049) during organ culture. There was, however, no evidence of PRL secretion into the culture medium as measured by ELISA. PRL immunoreactivity (IR) in female human epidermis was decreased by substance P (p?=?0.009), while neither the classical pituitary PRL inhibitor, dopamine, nor corticotropin-releasing hormone significantly modulated PRL IR in HFs or skin respectively. Interferon (IFN) ? increased PRL IR in the epithelium of human HFs (p?=?0.044) while tumour necrosis factor (TNF) ? decreased both PRL and PRLR IR. This study identifies substance P, TNF? and IFN? as novel modulators of PRL and PRLR expression in human skin, and suggests that intracutaneous PRL expression is not under dopaminergic control. Given the importance of PRL in human hair growth regulation and its possible role in the pathogenesis of several common skin diseases, targeting intracutaneous PRL production via these newly identified regulatory pathways may point towards novel therapeutic options for inflammatory dermatoses.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:PLoS One. - 8 : 4 (2013), p. e60819. -
További szerzők:Vidali, Silvia Pigat, Natascha Funk, Wolfgang Lisztes Erika (1986-) (élettanász) Bíró Tamás (1968-) (élettanász) Goffin, Vincent Griffiths, Christopher E. M. Paus, Ralf
Internet cím:DOI
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3.

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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