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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.
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