β1 integrin signaling maintains human epithelial progenitor cell survival in situ and controls proliferation, apoptosis and migration of their progeny.

β1 integrin regulates multiple epithelial cell functions by connecting cells with the extracellular matrix (ECM). While β1 integrin-mediated signaling in murine epithelial stem cells is well-studied, its role in human adult epithelial progenitor cells (ePCs) in situ remains to be defined. Using micr...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Nancy Ernst, Arzu Yay, Tamás Bíró, Stephan Tiede, Martin Humphries, Ralf Paus, Jennifer E Kloepper
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/42510628733a437d971971fe3a74d93b
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:42510628733a437d971971fe3a74d93b
record_format	dspace
spelling	oai:doaj.org-article:42510628733a437d971971fe3a74d93b2021-11-18T08:40:05Zβ1 integrin signaling maintains human epithelial progenitor cell survival in situ and controls proliferation, apoptosis and migration of their progeny.1932-620310.1371/journal.pone.0084356https://doaj.org/article/42510628733a437d971971fe3a74d93b2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24386370/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203β1 integrin regulates multiple epithelial cell functions by connecting cells with the extracellular matrix (ECM). While β1 integrin-mediated signaling in murine epithelial stem cells is well-studied, its role in human adult epithelial progenitor cells (ePCs) in situ remains to be defined. Using microdissected, organ-cultured human scalp hair follicles (HFs) as a clinically relevant model for studying human ePCs within their natural topobiological habitat, β1 integrin-mediated signaling in ePC biology was explored by β1 integrin siRNA silencing, specific β1 integrin-binding antibodies and pharmacological inhibition of integrin-linked kinase (ILK), a key component of the integrin-induced signaling cascade. β1 integrin knock down reduced keratin 15 (K15) expression 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 HF mesenchyme significantly enhanced proliferation and migration of ORSKs, while K15 and CD200 gene and protein expression were inhibited. Employing ECM-embedded β1 integrin-activating or -inhibiting antibodies allowed to identify functionally distinct human ePC subpopulations in different compartments of the HF epithelium. The β1 integrin-inhibitory antibody reduced β1 integrin expression in situ and selectively enhanced proliferation of bulge ePCs, while the β1 integrin-stimulating antibody decreased hair matrix keratinocyte apoptosis and enhanced transferrin receptor (CD71) immunoreactivity, a marker of transit amplifying cells, but did not affect bulge ePC proliferation. That the putative ILK inhibitor QLT0267 significantly reduced ORSK migration and proliferation and induced massive ORSK apoptosis suggests a key role for ILK in mediating the ß1 integrin effects. Taken together, these findings demonstrate that ePCs in human HFs require β1 integrin-mediated signaling for survival, adhesion, and migration, and that different human HF ePC subpopulations differ in their response to β1 integrin signaling. These insights may be exploited for cell-based regenerative medicine strategies that employ human HF-derived ePCs.Nancy ErnstArzu YayTamás BíróStephan TiedeMartin HumphriesRalf PausJennifer E KloepperPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 12, p e84356 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Nancy Ernst Arzu Yay Tamás Bíró Stephan Tiede Martin Humphries Ralf Paus Jennifer E Kloepper β1 integrin signaling maintains human epithelial progenitor cell survival in situ and controls proliferation, apoptosis and migration of their progeny.
description	β1 integrin regulates multiple epithelial cell functions by connecting cells with the extracellular matrix (ECM). While β1 integrin-mediated signaling in murine epithelial stem cells is well-studied, its role in human adult epithelial progenitor cells (ePCs) in situ remains to be defined. Using microdissected, organ-cultured human scalp hair follicles (HFs) as a clinically relevant model for studying human ePCs within their natural topobiological habitat, β1 integrin-mediated signaling in ePC biology was explored by β1 integrin siRNA silencing, specific β1 integrin-binding antibodies and pharmacological inhibition of integrin-linked kinase (ILK), a key component of the integrin-induced signaling cascade. β1 integrin knock down reduced keratin 15 (K15) expression 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 HF mesenchyme significantly enhanced proliferation and migration of ORSKs, while K15 and CD200 gene and protein expression were inhibited. Employing ECM-embedded β1 integrin-activating or -inhibiting antibodies allowed to identify functionally distinct human ePC subpopulations in different compartments of the HF epithelium. The β1 integrin-inhibitory antibody reduced β1 integrin expression in situ and selectively enhanced proliferation of bulge ePCs, while the β1 integrin-stimulating antibody decreased hair matrix keratinocyte apoptosis and enhanced transferrin receptor (CD71) immunoreactivity, a marker of transit amplifying cells, but did not affect bulge ePC proliferation. That the putative ILK inhibitor QLT0267 significantly reduced ORSK migration and proliferation and induced massive ORSK apoptosis suggests a key role for ILK in mediating the ß1 integrin effects. Taken together, these findings demonstrate that ePCs in human HFs require β1 integrin-mediated signaling for survival, adhesion, and migration, and that different human HF ePC subpopulations differ in their response to β1 integrin signaling. These insights may be exploited for cell-based regenerative medicine strategies that employ human HF-derived ePCs.
format	article
author	Nancy Ernst Arzu Yay Tamás Bíró Stephan Tiede Martin Humphries Ralf Paus Jennifer E Kloepper
author_facet	Nancy Ernst Arzu Yay Tamás Bíró Stephan Tiede Martin Humphries Ralf Paus Jennifer E Kloepper
author_sort	Nancy Ernst
title	β1 integrin signaling maintains human epithelial progenitor cell survival in situ and controls proliferation, apoptosis and migration of their progeny.
title_short	β1 integrin signaling maintains human epithelial progenitor cell survival in situ and controls proliferation, apoptosis and migration of their progeny.
title_full	β1 integrin signaling maintains human epithelial progenitor cell survival in situ and controls proliferation, apoptosis and migration of their progeny.
title_fullStr	β1 integrin signaling maintains human epithelial progenitor cell survival in situ and controls proliferation, apoptosis and migration of their progeny.
title_full_unstemmed	β1 integrin signaling maintains human epithelial progenitor cell survival in situ and controls proliferation, apoptosis and migration of their progeny.
title_sort	β1 integrin signaling maintains human epithelial progenitor cell survival in situ and controls proliferation, apoptosis and migration of their progeny.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/42510628733a437d971971fe3a74d93b
work_keys_str_mv	AT nancyernst b1integrinsignalingmaintainshumanepithelialprogenitorcellsurvivalinsituandcontrolsproliferationapoptosisandmigrationoftheirprogeny AT arzuyay b1integrinsignalingmaintainshumanepithelialprogenitorcellsurvivalinsituandcontrolsproliferationapoptosisandmigrationoftheirprogeny AT tamasbiro b1integrinsignalingmaintainshumanepithelialprogenitorcellsurvivalinsituandcontrolsproliferationapoptosisandmigrationoftheirprogeny AT stephantiede b1integrinsignalingmaintainshumanepithelialprogenitorcellsurvivalinsituandcontrolsproliferationapoptosisandmigrationoftheirprogeny AT martinhumphries b1integrinsignalingmaintainshumanepithelialprogenitorcellsurvivalinsituandcontrolsproliferationapoptosisandmigrationoftheirprogeny AT ralfpaus b1integrinsignalingmaintainshumanepithelialprogenitorcellsurvivalinsituandcontrolsproliferationapoptosisandmigrationoftheirprogeny AT jenniferekloepper b1integrinsignalingmaintainshumanepithelialprogenitorcellsurvivalinsituandcontrolsproliferationapoptosisandmigrationoftheirprogeny
_version_	1718421496555110400

β1 integrin signaling maintains human epithelial progenitor cell survival in situ and controls proliferation, apoptosis and migration of their progeny.

Ejemplares similares