Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

0

Conditional keratinocyte-specific ADAM17 knockout in mice alters skin homeostasis


ABSTRACT: This study investigates the role of ADAM17 (a disintegrin and metalloproteinase 17) in skin homeostasis. Here, we show that mice lacking ADAM17 in keratinocytes have a normal epidermal barrier and skin architecture at birth, but develop pronounced defects in epidermal barrier integrity soon after birth and chronic dermatitis as adults. The dysregulated expression of epidermal differentiation proteins becomes evident 2 days after birth, followed by transepidermal water loss and inflammatory immune cell infiltration. Our results identify a previously unappreciated critical role of the ADAM17/EGFR signaling axis in maintaining the homeostasis of the postnatal epidermal barrier. The genome-wide effects of ADAM17 deficiency were analyzed using Agilent Whole Mouse Genome microarrays. Conditional keratinocyte-specific ADAM17 knockout mice were generated by crossing Adam17flox/flox mice with keratin-14-Cre (Krt14-Cre) transgenic mice. Adam17flox/+Krt14-Cre mice were mated with Adam17flox/flox mice to generate pups of Adam17flox/flox Krt14-Cre positive (cKO) and Krt14-Cre negative (wild-type) control littermates. The genetic background was a mix of 129Sv and C57BL/6. As material, back skin tissue biopsies (postnatal day 10) from n = 2 wild-type skin and n = 2 ADAM17 epidermal KO skin (matched WT-cKO pairs from two different litters) were used in this study.

ORGANISM(S): Mus musculus

SUBMITTER: Claus-Werner Franzke 

PROVIDER: E-GEOD-38830 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

altmetric image

Publications

Epidermal ADAM17 maintains the skin barrier by regulating EGFR ligand-dependent terminal keratinocyte differentiation.

Franzke Claus-Werner CW   Cobzaru Cristina C   Triantafyllopoulou Antigoni A   Löffek Stefanie S   Horiuchi Keisuke K   Threadgill David W DW   Kurz Thomas T   van Rooijen Nico N   Bruckner-Tuderman Leena L   Blobel Carl P CP  

The Journal of experimental medicine 20120507 6


ADAM17 (a disintegrin and metalloproteinase 17) is ubiquitously expressed and cleaves membrane proteins, such as epidermal growth factor receptor (EGFR) ligands, l-selectin, and TNF, from the cell surface, thus regulating responses to tissue injury and inflammation. However, little is currently known about its role in skin homeostasis. We show that mice lacking ADAM17 in keratinocytes (A17(ΔKC)) have a normal epidermal barrier and skin architecture at birth but develop pronounced defects in epid  ...[more]

Similar Datasets

2012-06-21 | GSE38830 | GEO
2018-05-01 | GSE107687 | GEO
2016-04-20 | PXD002597 | Pride
2008-06-20 | E-GEOD-10728 | biostudies-arrayexpress
2019-06-10 | MSV000083953 | MassIVE
2021-03-09 | GSE148521 | GEO
2011-01-20 | E-GEOD-25548 | biostudies-arrayexpress
2020-06-28 | E-MTAB-9235 | biostudies-arrayexpress
2008-06-20 | E-GEOD-10726 | biostudies-arrayexpress
2012-01-18 | E-GEOD-35129 | biostudies-arrayexpress