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Perlecan expression influences the keratin 15‐positive cell population fate in the epidermis of aging skin

Identifieur interne : 000713 ( Pmc/Checkpoint ); précédent : 000712; suivant : 000714

Perlecan expression influences the keratin 15‐positive cell population fate in the epidermis of aging skin

Auteurs : Morgan Dos Santos [France] ; Anna Michopoulou [France] ; Valérie André-Frei [France] ; Sophie Boulesteix [France] ; Christine Guicher [France] ; Guila Dayan [France] ; John Whitelock [Australie] ; Odile Damour [France] ; Patricia Rousselle [France]

Source :

RBID : PMC:4925826

Abstract

The epidermis is continuously renewed by stem cell proliferation and differentiation. Basal keratinocytes append the dermal‐epidermal junction, a cell surface‐associated, extracellular matrix that provides structural support and influences their behaviour. It consists of laminins, type IV collagen, nidogens, and perlecan, which are necessary for tissue organization and structural integrity. Perlecan is a heparan sulfate proteoglycan known to be involved in keratinocyte survival and differentiation. Aging affects the dermal epidermal junction resulting in decreased contact with keratinocytes, thus impacting epidermal renewal and homeostasis. We found that perlecan expression decreased during chronological skin aging. Our in vitro studies revealed reduced perlecan transcript levels in aged keratinocytes. The production of in vitro skin models revealed that aged keratinocytes formed a thin and poorly organized epidermis. Supplementing these models with purified perlecan reversed the phenomenon allowing restoration of a well‐differentiated multi‐layered epithelium. Perlecan down‐regulation in cultured keratinocytes caused depletion of the cell population that expressed keratin 15. This phenomenon depended on the perlecan heparan sulphate moieties, which suggested the involvement of a growth factor. Finally, we found defects in keratin 15 expression in the epidermis of aging skin. This study highlighted a new role for perlecan in maintaining the self‐renewal capacity of basal keratinocytes.


Url:
DOI: 10.18632/aging.100928
PubMed: 26996820
PubMed Central: 4925826


Affiliations:


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PMC:4925826

Le document en format XML

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<p>The epidermis is continuously renewed by stem cell proliferation and differentiation. Basal keratinocytes append the dermal‐epidermal junction, a cell surface‐associated, extracellular matrix that provides structural support and influences their behaviour. It consists of laminins, type IV collagen, nidogens, and perlecan, which are necessary for tissue organization and structural integrity. Perlecan is a heparan sulfate proteoglycan known to be involved in keratinocyte survival and differentiation. Aging affects the dermal epidermal junction resulting in decreased contact with keratinocytes, thus impacting epidermal renewal and homeostasis. We found that perlecan expression decreased during chronological skin aging. Our in vitro studies revealed reduced perlecan transcript levels in aged keratinocytes. The production of in vitro skin models revealed that aged keratinocytes formed a thin and poorly organized epidermis. Supplementing these models with purified perlecan reversed the phenomenon allowing restoration of a well‐differentiated multi‐layered epithelium. Perlecan down‐regulation in cultured keratinocytes caused depletion of the cell population that expressed keratin 15. This phenomenon depended on the perlecan heparan sulphate moieties, which suggested the involvement of a growth factor. Finally, we found defects in keratin 15 expression in the epidermis of aging skin. This study highlighted a new role for perlecan in maintaining the self‐renewal capacity of basal keratinocytes.</p>
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<pmc article-type="research-article">
<pmc-dir>properties open_access</pmc-dir>
<front>
<journal-meta>
<journal-id journal-id-type="nlm-ta">Aging (Albany NY)</journal-id>
<journal-id journal-id-type="iso-abbrev">Aging (Albany NY)</journal-id>
<journal-id journal-id-type="publisher-id">Aging</journal-id>
<journal-id journal-id-type="publisher-id">ImpactJ</journal-id>
<journal-title-group>
<journal-title>Aging (Albany NY)</journal-title>
</journal-title-group>
<issn pub-type="epub">1945-4589</issn>
<publisher>
<publisher-name>Impact Journals LLC</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="pmid">26996820</article-id>
<article-id pub-id-type="pmc">4925826</article-id>
<article-id pub-id-type="publisher-id">100928</article-id>
<article-id pub-id-type="doi">10.18632/aging.100928</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Research Paper</subject>
</subj-group>
</article-categories>
<title-group>
<article-title>Perlecan expression influences the keratin 15‐positive cell population fate in the epidermis of aging skin</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name>
<surname>Dos Santos</surname>
<given-names>Morgan</given-names>
</name>
<xref ref-type="aff" rid="A1">
<sup>1</sup>
</xref>
<xref ref-type="aff" rid="A2">
<sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Michopoulou</surname>
<given-names>Anna</given-names>
</name>
<xref ref-type="aff" rid="A1">
<sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>André‐Frei</surname>
<given-names>Valérie</given-names>
</name>
<xref ref-type="aff" rid="A2">
<sup>2</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Boulesteix</surname>
<given-names>Sophie</given-names>
</name>
<xref ref-type="aff" rid="A1">
<sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Guicher</surname>
<given-names>Christine</given-names>
</name>
<xref ref-type="aff" rid="A1">
<sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Dayan</surname>
<given-names>Guila</given-names>
</name>
<xref ref-type="aff" rid="A1">
<sup>1</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Whitelock</surname>
<given-names>John</given-names>
</name>
<xref ref-type="aff" rid="A3">
<sup>3</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Damour</surname>
<given-names>Odile</given-names>
</name>
<xref ref-type="aff" rid="A1">
<sup>1</sup>
</xref>
<xref ref-type="aff" rid="A4">
<sup>4</sup>
</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Rousselle</surname>
<given-names>Patricia</given-names>
</name>
<xref ref-type="aff" rid="A1">
<sup>1</sup>
</xref>
</contrib>
</contrib-group>
<aff id="A1">
<sup>1</sup>
Laboratoire de Biologie Tissulaire et Ingénierie Thérapeutique, UMR 5305, CNRS, University Lyon 1, Lyon, France</aff>
<aff id="A2">
<sup>2</sup>
BASF BCS France SAS, 69366, Lyon, France</aff>
<aff id="A3">
<sup>3</sup>
Graduate School of Biomedical Engineering, University of New South Wales Sydney, Australia</aff>
<aff id="A4">
<sup>4</sup>
Cell and Tissue Bank, Hôpital Edouard Herriot, Lyon, France</aff>
<author-notes>
<corresp id="cor1">
<bold>
<italic>Correspondence to:</italic>
</bold>
<italic>Patricia Rousselle</italic>
<email>patricia.rousselle@ibcp.fr</email>
</corresp>
</author-notes>
<pub-date pub-type="collection">
<month>4</month>
<year>2016</year>
</pub-date>
<pub-date pub-type="epub">
<day>17</day>
<month>3</month>
<year>2016</year>
</pub-date>
<volume>8</volume>
<issue>4</issue>
<fpage>751</fpage>
<lpage>768</lpage>
<history>
<date date-type="received">
<day>13</day>
<month>1</month>
<year>2016</year>
</date>
<date date-type="accepted">
<day>23</day>
<month>2</month>
<year>2016</year>
</date>
</history>
<permissions>
<copyright-statement>Copyright: © 2016 Dos Santos et al.</copyright-statement>
<copyright-year>2016</copyright-year>
<license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by/2.5/">
<license-p>This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</license-p>
</license>
</permissions>
<abstract>
<p>The epidermis is continuously renewed by stem cell proliferation and differentiation. Basal keratinocytes append the dermal‐epidermal junction, a cell surface‐associated, extracellular matrix that provides structural support and influences their behaviour. It consists of laminins, type IV collagen, nidogens, and perlecan, which are necessary for tissue organization and structural integrity. Perlecan is a heparan sulfate proteoglycan known to be involved in keratinocyte survival and differentiation. Aging affects the dermal epidermal junction resulting in decreased contact with keratinocytes, thus impacting epidermal renewal and homeostasis. We found that perlecan expression decreased during chronological skin aging. Our in vitro studies revealed reduced perlecan transcript levels in aged keratinocytes. The production of in vitro skin models revealed that aged keratinocytes formed a thin and poorly organized epidermis. Supplementing these models with purified perlecan reversed the phenomenon allowing restoration of a well‐differentiated multi‐layered epithelium. Perlecan down‐regulation in cultured keratinocytes caused depletion of the cell population that expressed keratin 15. This phenomenon depended on the perlecan heparan sulphate moieties, which suggested the involvement of a growth factor. Finally, we found defects in keratin 15 expression in the epidermis of aging skin. This study highlighted a new role for perlecan in maintaining the self‐renewal capacity of basal keratinocytes.</p>
</abstract>
<kwd-group>
<kwd>basement membrane</kwd>
<kwd>perlecan</kwd>
<kwd>keratinocyte</kwd>
<kwd>skin aging</kwd>
<kwd>keratin 15</kwd>
<kwd>stem cell</kwd>
</kwd-group>
</article-meta>
</front>
</pmc>
<affiliations>
<list>
<country>
<li>Australie</li>
<li>France</li>
</country>
<region>
<li>Auvergne-Rhône-Alpes</li>
<li>Rhône-Alpes</li>
</region>
<settlement>
<li>Lyon</li>
</settlement>
</list>
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<country name="France">
<region name="Auvergne-Rhône-Alpes">
<name sortKey="Dos Santos, Morgan" sort="Dos Santos, Morgan" uniqKey="Dos Santos M" first="Morgan" last="Dos Santos">Morgan Dos Santos</name>
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<name sortKey="Andre Rei, Valerie" sort="Andre Rei, Valerie" uniqKey="Andre Rei V" first="Valérie" last="André-Frei">Valérie André-Frei</name>
<name sortKey="Boulesteix, Sophie" sort="Boulesteix, Sophie" uniqKey="Boulesteix S" first="Sophie" last="Boulesteix">Sophie Boulesteix</name>
<name sortKey="Damour, Odile" sort="Damour, Odile" uniqKey="Damour O" first="Odile" last="Damour">Odile Damour</name>
<name sortKey="Damour, Odile" sort="Damour, Odile" uniqKey="Damour O" first="Odile" last="Damour">Odile Damour</name>
<name sortKey="Dayan, Guila" sort="Dayan, Guila" uniqKey="Dayan G" first="Guila" last="Dayan">Guila Dayan</name>
<name sortKey="Dos Santos, Morgan" sort="Dos Santos, Morgan" uniqKey="Dos Santos M" first="Morgan" last="Dos Santos">Morgan Dos Santos</name>
<name sortKey="Guicher, Christine" sort="Guicher, Christine" uniqKey="Guicher C" first="Christine" last="Guicher">Christine Guicher</name>
<name sortKey="Michopoulou, Anna" sort="Michopoulou, Anna" uniqKey="Michopoulou A" first="Anna" last="Michopoulou">Anna Michopoulou</name>
<name sortKey="Rousselle, Patricia" sort="Rousselle, Patricia" uniqKey="Rousselle P" first="Patricia" last="Rousselle">Patricia Rousselle</name>
</country>
<country name="Australie">
<noRegion>
<name sortKey="Whitelock, John" sort="Whitelock, John" uniqKey="Whitelock J" first="John" last="Whitelock">John Whitelock</name>
</noRegion>
</country>
</tree>
</affiliations>
</record>

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